Registration Dossier

Administrative data

Description of key information

The acute dermal and oral toxicity of the test substance 6,6’-di-tert-butyl-2,2’-methylendi-p-cresol (DBMC) is very low, indicated by LD50 values greater than 5000 mg/kg. The acute oral LD50 value in rats is greater than 5000 mg/kg bw mg/kg (Takagi 1994) and the dermal LD50 value in rabbits is greater than 10000 mg/kg bw (American Cyanamid Company 1965). 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: limited but acceptable documented study report which meets basic scientific principles
Principles of method if other than guideline:
other: acute oral toxicity study
GLP compliance:
no
Test type:
other: acute oral toxicity study
Species:
rat
Strain:
other: Albino rats
Sex:
male
Route of administration:
oral: gavage
Vehicle:
water
Doses:
10000 mg/kg
No. of animals per sex per dose:
10 males
Control animals:
no
Sex:
male
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: clinical signs: depression

Mortality: no death occurred during the study

Clinical signs: depression, noted 6 to 24 h after test substance application, recovery 24 h after application

Gross autopsy: normal

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: limited but acceptable documented study report which meets basic scientific principles
Principles of method if other than guideline:
other: acute dermal toxicity study
GLP compliance:
no
Test type:
other: acute dermal toxicity study
Species:
rabbit
Strain:
other: Albino rabbit (no additional data given)
Sex:
male
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
10000 mg/kg bw
No. of animals per sex per dose:
5 males per dose
Control animals:
not required
Sex:
male
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality and clinical signs observed during the study

Mortality: none during the study (0/5)

Skin irritation: not observed during the study

Clinical signs: not observed during the study

Gross autopsy: normal

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
10 000 mg/kg bw

Additional information

Acute toxicity: oral

The oral toxicity of 6,6’-di-tert-butyl-2,2’-methylendi-p-cresol (DBMC) was evaluated in several studies with rats or mice. The available study data are limited compared to current guideline studies, but are acceptable well-documented and sufficient for risk assessment. In an acute oral toxicity study male and female Wistar rats were dosed once with 5000 mg/kg bw 6,6’-di-tert-butyl-2,2’-methylendi-p-cresol (Takagi 1994). The test substance suspended in olive oil (30% w/v) was administered to 5 male and five female rats. Toxic signs and mortality were monitored for 9 hrs on the day of administration and then twice a day up to day 14 when the test was terminated. Body weights were recorded at days 3, 7, 10 and 14 after administration. No mortality occurred during the study. Diarrhoea was observed 1 h after the administration of the test material or vehicle alone (controls). Diarrhoea disappeared within 1 day (controls) or 6 days (treatment group). No other clinical signs were indicated. In both sexes, no significant differences in body weight gain was observed between control and treated rats. An oral LD50 value greater 5000 mg/kg bw was suggested.

In another early acute oral toxicity study with male Albino rats (American Cyanamid Company 1965) an oral LD50 value greater than 10000 mg/kg bw was suggested. Further studies with rats and mice confirmed the very low acute oral toxicity of 6,6’-di-tert-butyl-2,2’-methylendi-p-cresol indicated by LD50 values greater than 5000 mg/kg bw (Hagan 1952, Garlanda 1962, Stasenkova 1977).

Acute toxicity: dermal

The acute dermal toxicity of 6,6’-di-tert-butyl-2,2’-methylendi-p-cresol (DBMC) was evaluated in an early toxicity study with male albino rabbits (American Cyanamid Company 1965). However, the study design and documentation are not inline with current guidelines but the study is acceptable well-documented and sufficient for risk assessment. Five male rabbits were exposed with 10000 mg/kg test substance for 24 hours, followed by a 14day-observation period. No mortality and clinical signs occurred during the study (0/5). No skin irritation was observed. Gross autopsy performed at study termination revealed no abnormalities. Based on the findings of this study the authors suggested a dermal LD50 greater than 10000 mg/kg bw.

Justification for classification or non-classification

No classification is required according to the classification criteria 67/548/EWG and regulation no. 1272/2008 (GHS).