Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
other: component of reaction mass
Adequacy of study:
key study
Study period:
from 1998-11-10 to 1999-11-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD TG 401 and EU Method B.1

Data source

Reference
Reference Type:
secondary source
Title:
No information
Author:
ECHA disseminated dossier
Year:
1999
Bibliographic source:
Dossier EC 905-013-3
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes (incl. QA statement)
Remarks:
The Department of Health of the Government of the United Kingdom, 23rd March 1998
Limit test:
no

Test material

Constituent 1
Reference substance name:
Isomenthone
EC Number:
207-727-4
EC Name:
Isomenthone
Cas Number:
491-07-6
IUPAC Name:
2-isopropyl-5-methylcyclohexanone
Test material form:
other: colourless liquid
Details on test material:
- Name of test material (as cited in study report): Isomenthon

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: eight to twelve weeks old
- Weight at study initiation: 214-246 g (males), 201-236 g (females)
- Fasting period before study: an overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: in groups of up to five by sex
- Diet (e.g. ad libitum): (Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK, ad libitum
- Water (e.g. ad libitum): mains drinking water, ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1999-09-09 To: 1999-10-12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.24 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: based on the results of the range-finding study
Doses:
1000, 1414 and 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14 or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross lesions and other toxicological effects
Statistics:
LD50 and 95% confidence limits were calculated by the method of Thompson. (Thompson, W.R., Bact. Reviews, 11, 115-145 (1947

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
2 119 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 322 - <= 3 396
Mortality:
2 out of 5 female rats and 1 out of 5 male rats of highest dose died one and two days after dosing. One female animal treated with 2000 mg/kg was killed in extremis one day after dosing.
Clinical signs:
Clinical signs of toxicity commonly noted in all dose groups were hunched posture and lethargy. Ataxia was noted in animals treated with 1414 or 2000 mg/kg. Decreased respiratory rate and laboured respiration were noted in animals treated with 1000 or 2000 mg/kg. Ptosis was commonly noted in animals treated with 2000 mg/kg with incidents of loss of righting reflex. An isolated incident of redlbrown staining around the eyes was noted in one animal treated with 1414 mg/kg. Incidents of toxicity noted in female animals treated with 2000 mg/kg were increased lacrimation, pilo-erection and splayed or tiptoe gait. One female animal treated with 2000 mg/kg was comatose prior to killing in extremis. Surviving animals recovered one to four days after dosing.
Body weight:
Surviving animals showed expected gain in bodyweight during the study.
Gross pathology:
Abnormalities noted at necropsy of the animal that was killed in extremis or animals that died during the study were haemorrhagic or abnormally red lungs, pale liver or patchy pallor of the liver, dark kidneys, slightly haemorrhagic or pale gastric mucosa, sloughing of the non-glandular epithelium of the stomach and haemorrhage of the small and large intestines. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of the test material, Isomenthone, in the Sprague-Dawley CD strain female rat was 2119 mg/kg body weight. Male animals were considered not to be markedly more sensitive to the test material than female animals.
Executive summary:

The acute oral toxicity of the test substance Isomenthone was studied in a GLP test according to OECD TG 401 and EU Method B.1. Groups of five animals were exposed to single oral (gavage) doses of 1000, 1414 and 2000 mg/kg bw in females and of 2000 mg/kg bw in males. Animals were observed during a period of 14 days. No mortality was observed in the low ad the mid-dose groups, whereas 2 females and 1 male of the high-dose group died within one and two days after dosing. One female animal

treated with 2000 mg/kg bw was killed in extremis one day after dosing. The LD50 and 95 % confidence limits were calculated by the method of Thompson. (Thompson, W.R., Bact. Reviews, 11, 115-145 (1947).)

The LD50 value for females was 2119 mg/kg bw with a 95 % confidence interval of 1322 to 3396 mg/kg bw. Male animals were considered not to be markedly more sensitive to the test material than female animals. Clinical signs of toxicity were ataxia, hunched posture, lethargy, increased lacrimation, pilo-erection, ptosis, decreased respiratory rate, laboured respiration, redlbrown staining around the eyes, loss of righting reflex and splayed or tiptoe gait. Surviving animals recovered one to four days after dosing.

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