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PubMed1997

Study on the developmental toxicity of orally administered isobutylidenediurea in rats.

Developmental toxicity of isobutylidenediurea (IBDU) was determined by oral administration to Wistar rats. The substance was administered as an aqueous suspension to 22-24 pregnant rats per group by gavage in daily doses of 100, 400 and 1000 mg/kg body weight from day 6 post-coitum (p.c.) to day 15 p.c. The control group received the vehicle only (0.5% aqueous carboxymethyl cellulose solution). There were no substance-related effects in the dams concerning food consumption, body weight, body weight gain, uterine weights and clinical or autopsy observations even at the highest dose of 1000 mg/kg body weight/day. The reproduction data revealed no biologically relevant differences between the control and treated groups. The incidence and type of the foetal external, soft tissue and skeletal findings, which were classified as malformations, variations and/or retardations observed in the treated foetuses were similar to the concurrent and/or historical control data. Thus, under the conditions of this study, no signs of maternal toxicity or embryo/foetotoxicity were induced by IBDU and the no-observable-adverse-effect level on the maternal and developing organism was 1000 mg/kg body weight/day.

Abnormalities, Drug-Induced↗
PubMed2001

Isobutylidenediurea degradation by Rhodococcus erythropolis.

A new enzyme (isobutylidenediurea amidinohydrolase) catalyzing the hydrolysis of isobutylidenediurea (a condensation product of urea and isobutyraldehyde widely used as a slow-release nitrogeneous fertilizer) was characterized from a strain of Rhodococcus erythropolis. The enzyme was purified 1,250-fold to apparent homogeneity and shown to hydrolyze the fertilizer to urea and isobutyraldehyde at a molar ratio of 2: 1. No activity was observed with ureido- or other structurally related compounds. Its molecular mass was determined by native polyacrylamide gelelectrophoresis and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry to be 15 kDa (+/-2 kDa) and 16.4 kDa, respectively. Growth of the bacterium in the presence of isobutylidenediurea led to an increased expression of the constitutively synthetized enzyme.

Biodegradation, Environmental↗
PubMed1976

[Isobutylene diurea as a new source of NPN for ruminants. 1. Nitrogen balance and plasma amino acid composition after feeding of isobutylene diurea to sheep].

The paper first presents a survey of the existing literature where studies on the effects of isobutylidene diurea (IBDH) as NPN source for ruminants are discussed. Following this the authors discuss their own experiments on IBDH turnover. IBDH showed no toxi cation when tested in toxicity studies with rats which were carried out under standardized conditions. Within the framework of metabolism trial 4 growing male sheep (average liveweight: 30 kg) were fed a semisynthetic diet containing IBDH as sole N source. Each animal received 60 g IBDH per day. The average value for the apparent N digestibility was found to be 77.6%, the percentage for the average N ballance was 27.6%. The blood of the sheep was investigated, on a comparative basis, for the behaviour of free amino acids after the administration of an experimental semisynthetic diet containing IBDH or extracted soya bean meal as sole N source. The use of IBDH produced a higher concentration of free amino acids and a five-fold increase if urea concentrations in the blood plasma but reduced the Asp, Cys and Tyr levels when compared with the feeding of extracted soya bean meal. Similarly, IBDH supplementation increased the relative proportions of Gly, Lys, and His in blood plasma but reduced those of Asp, Val and Tyr. A positive relationship between the rate of IBDH hydrolysis and the decrease in pH was found in experiments studying the hydrolysis behaviour of IBDH at pH values from 1-7.

Amino Acids↗
PubMed1977

[Isobutylidene diurea, a new NPN source for ruminants. 3. Excretion of isobutylidene diurea following feeding of N-15 isobutylidene diurea to lactating cows].

2 experimental cows received isobutylidenedi urea added to a natural diet in amounts of 175 g (I) and 730 g (II) per day for a period of several weeks before the trial was started. On the 1st day of experiment the morning dose was labelled with 5.05 g of excess 15N. 8 hrs after the beginning of the trial of 15N level in the TCE soluble portion of blood plasma (TCE=trichloroacetic acid) increased and remained at an elevated level until the 36th hour of experiment. Similarly, the values for maximum urinary 15N concentrations were maintained for a prolonged period of time. Isobutylidenedi urea was excreted with the urine in rates related to its solubility. Only small percentages of the 15N intake were excreted in the TCE soluble portion of the milk (cow I: 0.03%; cow II: 0.05%). The 15N-labelling of milk protein provides evidence for the fact that nitrogen from IBDU is utilized for the synthesis of milk in the cows. The amount of urea in milk averaged 400 mg per litre. None of the milk samples tested contained IBDU.

Animal Feed↗
PubMed1978

[Dynamics of 15N-isobutylidene diurea (IBDU) in sheep. 1. IBDU conversion in the digestive tract].

Four Merino Landrace wethers averaging 47.6 kg body weight were adapted to a semi-synthetic diet containing as the only N-source 60 g of IBDU per day. After the adaptation phase, on the 1 st experimental day the IBDU of the morning feed was given in 15N-labelled form (701 mg 15N-excess). After 2 1/2, 7 1/4, 12 and 24 hours the experimental animals were killed without having been fed again. The comparison of the IBDU-concentrations in the content of the rumen bottom with the residual rumen content did not allow to draw conclusions regarding IBDU-sedimentation at the bottom of the rumen. For the 15N-decline in the rumen content, a relationship was established following y = 76.3 - 2.62 (r = 0.96) (see fig. 2). In the order of killing times the following 15N-IBDU amounts were retrieved (% of intake): I = 15.6%, II = 24.1%, III = 3.3% and IV = 3.6%. 7 1/4 hours after starting the experiment, 40% of the 15N-labelled material were found in the rumen in the form IBDU; after 12 hours it came to 10%. Except for sheep I, 15N-urea was not found but in small amounts. Only sheep I and III revealed IBDU-traces in the abomasum, but in the small intestine of all sheep 2 to 6% of the amount taken in. This fact is explained with the endogenous influx of IBDU from the blood. An additional experimental sheep provided with a ligature at the abomasum entry, revealed that IBDU is absorbed from the rumen and allowed to enter the individual segments of the intestine in small amounts.

Animals↗
PubMed1981

[Isobutylidene diurea as an NPN source for ruminants. 1. Rumen fermentation, digestibility of the nutrients and microbial protein synthesis in dairy cows].

In 3 experiments 2 lactating dairy cows received a mixed ration consisting of 10 kg maize silage, 2.5 kg hay, 2.0 kg barley, 1 kg dried sugar-beet pulp, 1.5 kg maize starch, 0.5 kg sugar, 0.2 kg of a mineral-vitamin mixture and 0.08 kg non-protein nitrogen (NPN) per animal and day. The ration contained 8.3 kg dry matter, 5.1 kEFU cattle and 1.18 kg crude protein, 0.5 kg of which from NPN, and was given in equal shares twice a day. Urea (I) or isobutylidene diurea (IBDU), to which the animals were not adapted (II) resp. adapted (III), were the sources of NPN.IBDU proved to a be a very slow source of NH3 in the rumen. 2 hours after the intake of NPN 48 . . . 75, 5 . . . 9 and 5 . . . 12 mg NH3/100 ml could be detected from I to III. Up to the third hour the concentration of IBDU and urea increased in III, which is due to the slow distribution of the slowly soluble IBDU in the fluid digestaphasis. 12 hours after the feeding the level of IBDU and urea in III still amounted to 25 mg urea/100 ml, in I to 1 mg/100 ml only. In the first 3 hours after supplying the NPN the pH-value of I was more than 1 unit higher than that of II and III. There were no significant differences in the fermentation models between the variants, the concentration of volatile fatty acids was 12.6, 12.3 and 11.1 mmol/100 ml. In the stomachs the digestibility of the organic matter was 52, 51 and 54%, that of the crude cellulose 64, 62 and 66% and that of the starch 91, 93 and 98%. At the duodenum the passage rate of N was 87 . . . 93, 107 . . . 126 and 96 . . . 130% of the N-intake, that of NH3-N 6, 43 and 22 g per day and that of bacteria-N 61 . . . 76, 78 . . . 100 and 76 . . . 96% of the N-intake. 2.3 . . . 2.8, 2.6 . . . 3.2 and 2.1 . . . 3.1 g bacteria-N were formed per 100 g dry matter fermented in the rumen. In the intestines 55 . . . 61, 57 . . . 64 and 48 . . . 71% of the feed-N were available as non-NH3-N. The conclusion is that in comparison to urea and concerning IBDU, the rumeno-hepatic circulation plays a definitely bigger role for the N-supply of the rumen microbes and that the possibility of the better N-utilisation can be derived from that.

Animals↗
PubMed1981

[Isobutylidene urea as NPN source for ruminants. 2. Digestion of 15N-labeled isobutylidene urea in lactating dairy cows].

Two cows with rumen cannulae and duodenal re-entrance cannulae received in the first experiment (Ia and IIa) a conventional diet on the basis of a mixture of maize silage, hay and concentrated feed and after a three-week adaptation to isobutylidene diurea (IBDU)--276 g per animal and day--138 g IBDU with 3.865 mg 15N-excess as a single supplementation to their first meal. In the second experiment (IIa and IIb) after a 6-week break the same cows served a repeated experiment without IBDU adaptation. Irrespective of the adaptation, a re-increase of the 15N-labelling in the TCA-soluble N in the rumen could be proved between the 6th and the 8th hour after the intake of the isotopes, which resulted from the backflow of 15N to the rumen. In the duodenal digesta the maximum labelling of the TCA--soluble N-fraction appeared 12 hours after the intake of the isotopes. At that moment a labelling plateau began in the protein fraction, which lasted to the 36th hour. On an average of all 4 cows approximately 30% of the 15N taken in the TCA-precipitable fraction and 55 and 60% in the TCA-soluble fraction had passed the duodenum up to the 72nd hour after the beginning of the experiment. Up to the 72nd hour after the beginning of the experiment, approximately 15% were excreted in urine, approximately 16% in feces and approximately 7% in the milk. This shows that roughly one half of the 90% 15N-amount measured at its passage in the re-entrance cannula (related to the intake) was metabolised in the rumen at least twice, resp. after the first passage through the duodenum it originated from the intermediary metabolism (e.g. as amino acids and their incorporation as digestion secretions). Negative correlations could be ascertained between the pH-value of the rumen fluid and the 15N incorporation in the rumen proteins as well as 15N-excretion through the TCA-soluble and -precipitable quota of feces. An adaptation to IBDU is obviously not necessary.

Animal Feed↗
PubMedDate not supplied

Some attempts to improve the nutritive value of urea for dairy cows. II. Its administration in a slightly soluble form: isobutylidene diurea (IBDU).

Isobutylidene diurea (IBDU) was tested against urea with regard to the ammonia release in the rumen, the amount and composition of the nitrogen fraction reaching the intestine, the nitrogen and energy balances and the performance of lactating cows. Maize silage was the basal feed in all experiments. The ammonia concentration in the rumen liquor was measured in two dry cows fitted with a permanent rumen cannula. The ammonia release was clearly restrained when IBDU was substituted for urea, and the peak values were of the same order as those found with soybean meal. Two dry cows fitted with a re-entrant cannula at 10 cm from the pylorus were fed with maize silage supplemented with increasing amounts of either urea or IBDU. The duodenal flow levelled off with urea, but it continued to rise with IBDU even when high amounts were added to the silage. However, a large fraction of this increase was in the form of ammonia, corresponding to 60% of the dietary nitrogen supplied by IBDU. The amount of non-ammonia nitrogen was also higher with IBDU. The nitrogen balance of lactating cows was not noticeably affected when IBDU instead of urea was added to the maize silage. In the same manner, the digestibility of the rations and their metabolizable energy supply were not significantly modified, and the milk productions were quite similar with the two N compounds, apart from the tendency to lower milk fat and milk protein productions.

Ammonia↗