Registration Dossier

Administrative data

Description of key information

There is no data available for diethyl butylmalonate (CAS # 133 -08 -4). For C&L purposes, the following data available for structurally similar substances cited in the 2006 OECD SIDS “malonic acid diesters” (UNEP Publications, Final 10/2006) is suitable for read across:

Dimethylmalonate, CAS # 108-59-8

OECD 422 NOAEL = 300 mg/kg 

Diethylmalonate, CAS # 105-53-3

Limited study with NOAEL in the only dose level tested

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subacute
Species:
rat

Mode of Action Analysis / Human Relevance Framework

Additional information

There is no data available for diethyl butylmalonate (CAS # 133 -08 -4). For C&L purposes, the following data available for structurally similar substances cited in the 2006 OECD SIDS “malonic acid diesters” (UNEP Publications, Final 10/2006) is suitable for read across:

Dimethylmalonate, CAS # 108-59-8

In a subacute combined repeated dose reproductionl/developmental screening test with DMM

according to OECD TG 422 and GLP, groups of 10 male and female Wistar rats received doses of

100, 300 and 1000 mg/kg bw per day by gavage once daily, 7 d per week. A high dose recovery and

recovery control group of 5 animals of each sex per group was also included in the study. Males

received the test item 2 weeks prior to mating, during the mating period and approximately 2 weeks

post mating, with a total of 39 treatment days. Females were treated 2 weeks prior to mating, during

the mating period, throughout pregnancy and up to lactation day 4. Recovery animals were treated

for 39 days followed by a post exposure observation period of 14 days. The animals were examined

daily for clinical signs and a FOB was performed in randomly selected 5 males and females of each

group at the end of the dosing period for males and during the lactation period for females. Body

weights were recorded at the beginning of the study, at last weekly thereafter and at termination. All

dams were weighed on gestation days 0, 7, 14, and 20 and lactation days 1 and 4. Food consumption

was recorded weekly. Standard hematology and clinical chemistry parameters were

determined in 5 randomly selected males and females of each group at the end of the premating

period and the recovery period respectively. Organ weights of liver, adrenals, kidneys, thymus,

spleen, brain, and heart were determined of 5 males and females of each group. Testes and

epididymis weights were determined of all adult males of each group. All adult animals and pups

were examined for any structural abnormalities and pathological changes. Standard histopathology

was performed on all major tissues of 5 males and 5 females of the control and high dose groups as

weIl as all animals of the recovery and recovery control groups. Livers and testes of 5 males and

females in the low and mid dose groups were also examined histopathologically. Stages of

spermatogenesis and interstitial testicular structure were determined additionally.

No treatment related effects were observed on clinical symptoms, performance in the FOB, body

weight and body weight gain, food consumption, clinical chemistry, hematology, organ weights or

gross pathology. In the histopathological examination livers of animals of both sexes in the high

dose group showed a significantly increased incidence of hepatocellular hypertrophy. Similar

changes were not observed in the high dose recovery group indicating reversibility of the effect. At

dose levels of 300 and 100 mg/kg bw per day no treatment related histopathological changes were

observed. The NOAEL for repeated dose toxicity is therefore 300 mg/kg bw (OECD SIDS, 2006)

Diethylmalonate, CAS # 105 -53 -3

For DEM a limited subchronic toxicity study was reported in the literature. Ten to 16 male and

female CD-rats received DEM in their diet for 90 days at dose leveis of 36 mg/kg bw per day for

males and 41 mg/kg bw per day for females. A comparable untreated group of rats served as

control. Details of the study were not reported. The authors report that no treatment related

differences were found between the two groups with regard to growth, food intake, hematological

and clinical chemistry parameters, blood-urea levels, organ weights and organ pathology

(Posternak, Lindner, and Vodoz, 1969 cited in OECD SIDS, 2006).

Justification for classification or non-classification

Based on the available data for read across substances Dimethylmalonate, CAS # 108-59-8 and Diethylmalonate, CAS # 105 -53 -3, there is no indication that Diethyl butylmalonate (CAS # 133 -08 -4) would require classification for repeated dose toxicity.