Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985-12-02 to 1985-12-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(1981)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
2,2,4(or 2,4,4)-Trimethylhexanedioic acid of Hüls AG, purity 87 %, impurities methylpentanedoic acid and methylbutanedioic acid not quantified

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ORGANISMS: 
- Strain: Bor: WISW (SPF TNO)
- Source: F. Winkelmann, Borchen (Germany)
- Weight at study initiation: 5 males mean 117 g, 5 females mean 108 g
- Controls: no
- Fasting period before study: 16 hours
- Diet: ad libitum, R10 special diet for rats, SSniff R
- Water: ad libitum, tap water
- Acclimation period: 4 - 8 days
ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 1 °C
- Humidity: 60 +/- 5 %
- Photoperiod: 12 hours artificial light, 12 hours dark
- Air changes: 15 per hour

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
ADMINISTRATION: 
- Preparation of test substance: heating to 60 °C in water bath
- Doses per time period: single dose (gavage) at 30-40 °C
- Volume administered or concentration: 3.70-5.87 ml/kg bw of undiluted  test substance
- Post dose observation period: 14 days
Doses:
3980; 5010; 6310 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
EXAMINATIONS:
- Body weights: before, and 1, 7, 14 days post dosing
- Clinical signs and mortality: within 6 hours after dosing, thereafter  daily
- Necropsy: all animals (macroscopic)
Statistics:
LD50 is generally determined according to Litchfield and Wilcoxon, reported with 95 % confidence limits.
Means of body weights were calcultated

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 900 mg/kg bw
95% CL:
>= 4 414 - <= 5 439
Mortality:
MORTALITY: 
- Number of deaths at each dose:    
3980 mg/kg bw: no deaths   
5010 mg/kg bw: 2 males, 4 females dead within 26 hours   
6310 mg/kg bw: 5 males, 5 females dead within 24 hours   
Clinical signs:
CLINICAL SIGNS: 
- 30-60 minutes after application: Rough skin, hunched posture, low  temperature, slowness, slight sedation and ataxia, and prone position. 
- Later: Tremor, moderate to severe sedation and ataxia, staggering,  convulsions, bloody noses and dark eyes. Surviving animals showed no  
symptoms 24 (low dose) - 48 hours (mid dose) after application. 
Body weight:
Body weight gain was not affected.
Gross pathology:
NECROPSY FINDINGS: 
- Animals that died during the study: Strong hyperemia of the mucosa of  the stomach and necrosis of the intestine mucosa; some necrosis on  
kidney, spleen and lungs.
- Surviving animals: Hyperemia of the gastric mucosa in some animals
Other findings:
no other findings

Any other information on results incl. tables

LD50 = 4900 (4414-5439) mg/kg bw

Applicant's summary and conclusion

Interpretation of results:
relatively harmless
Remarks:
Migrated information Criteria used for interpretation of results: other: EU Directive 67/548/EEC
Conclusions:
According to this study the LD50 value (oral) was determined to be 4900 mg/kg bw in rats for the test item 2,2,4(or 2,4,4)-trimethylhexanedioic acid.
Executive summary:

In a study according to OECD TG 401 (1981) the test item 2,2,4(or 2,4,4)-trimethylhexanedioic acid was applied once to 3 dose groups of rats (5 male and 5 female Wistar rats per dose group) in doses of 3980, 5010 and 6310 mg/kg bw undiluted at a temperature of 30 - 40 °C. The observation period was 14 days.

Some mid- and high-dose animals died within 26 hours after oral application of the test item.

Clinical signs 30 -60 minutes after application were rough fur, hunched posture, low  temperature, slowness, slight sedation and ataxia, and prone position.

Later the rats showed tremor, moderate to severe sedation and ataxia, staggering, convulsions, bloody noses and dark eyes.

Animals that died during the  study showed strong hyperemia of the mucosa of the stomach and necrosis of the intestine mucosa; some necrosis on kidney, spleen and lung.

Some surviving animals revealed hyperemia of the gastric mucosa.

The LD50 value (oral) was determined to be 4900 (4414 - 5539) mg/kg bw in rats for the test item 2,2,4(or 2,4,4)-trimethylhexanedioic acid.