Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: somewhat similar to OECD TG 401: LD50 > 5000 mg/kg bw.

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
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Pre-OECD, pre-GLP study, somewhat similar to OECD 401, without detailed documentation, result acceptable for assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Remarks:
Pre-OECD study, performed somewhat similar to OECD TG 401, reported without detailed documentation.
GLP compliance:
no
Remarks:
pre-GLP study
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
Not specified
Route of administration:
oral: unspecified
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10 animals per dose
Control animals:
no
Details on study design:
- Duration of observation period: 14 days
- Frequency of observations: daily
No further experimental details provided in the report.
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
Four of ten animals died, deaths were observed on day 2, 4, 6 and 7.
Clinical signs:
Enteritis and pneumonia
Interpretation of results:
other: not classified: criteria not met
Remarks:
according to EU CLP Regulation (EC) No. 1272/2008 and its amendments.
Conclusions:
The key acute oral toxicity test (Denine, 1973) presented in this study record showed an LD50 of >5000 mg/kg bw.
Based on this key study and additional available studies presented in the Endpoint Summary, all presenting LD50's > 2000 mg/kg bw, the substance does not need to be classified for acute oral toxicity according to EU CLP Regulation (EC) No. 1272/2008 and its amendments. However, note that classification is warranted for GHS based on the additional available study from Avon (1977) presenting a LD50 of 3690 mg/kg bw, resulting in acute oral toxicity hazard Category 5 classification.
Executive summary:

Acute oral toxicity was assessed in a pre-OECD, pre-GLP study in which 10 rats were administered the substance at a dose level of 5000 mg/kg bw. Four of ten animals died, deaths were observed on day 2, 4, 6 and 7. Clinical signs included enteritis and pneumonia. The acute oral LD50 for the substance in rats was determined to be greater than 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute oral toxicity:

Key study:

Acute oral toxicity was assessed in a pre-OECD, pre-GLP study in which 10 rats were administered the substance at a dose level of 5000 mg/kg bw. Four of ten animals died, deaths were observed on day 2, 4, 6 and 7. Clinical signs included enteritis and pneumonia. The acute oral LD50 for the substance in rats was determined to be greater than 5000 mg/kg bw.

 

Additional available data:

In an additional available rat study, presented in the RIFM database (Research Institute for Fragrance Materials) the acute toxicity of the substance was assessed when administered by oral intubation to 5 female rats per group (Avon, 1977). The calculated LD50 is 3690 mg/kg bw. The animals were administered the test material in absolute ethanol (or undiluted) and were observed for a total of 7 days. At 215 mg/kg bw no effects were observed and 0/5 animals died. At 464, 1000, 2150 and 4640 mg/kg bw, respectively 1, 0, 1 and 3 animals per group of 5 died. Clinical signs included depression, a depressed, lethargic condition and lethargy. Necropsy observations in the animals that died were reported to be characteristic of the various stages of autolysis.

In a mouse acute oral toxicity study (presented in the RIFM database), using groups of 10 animals, the LD50 was greater than 20000 mg/kg bw (Givaudan, 1963). At 20000, 7500, 5000, 4000 and 2000 mg/kg bw no effects and no deaths were observed during the 5-day observation period.

 

Acute dermal toxicity:

Additional available data:

Next to acute oral toxicity also acute dermal toxicity is assessed in the key study (Denine, 1973). A group of 6 rabbits were administered 5000 mg/kg bw test substance. None of the animals died and no clinical signs were reported. The acute dermal LD50 > 5000 mg/kg bw.

Furthermore, in the additional available study from Avon (1977) also acute dermal toxicity was assessed. The study was conducted in groups of 5 female rats using following dose levels: 464, 1000, 2150, 4640 and 10000 mg/kg bw. The acute dermal LD50 exceeded 10000 mg/kg bw: no animals died within the 7 day observation period.

The additional available acute dermal toxicity data, presenting LD50’s > 5000 mg/kg bw, does not warrant classification for EU CLP.

Justification for classification or non-classification

Acute oral toxicity:

Based on the key study and additional available studies, all presenting LD50's > 2000 mg/kg bw, the substance does not need to be classified for acute oral toxicity according to EU CLP (EC No. 1272/2008 and its amendments).

However, classification is warranted for GHS based on the additional available study from Avon (1977) presenting a LD50 of 3690 mg/kg bw, resulting in acute oral toxicity hazard Category 5 classification for GHS.