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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986-06-02 to 1986-06-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
This study was performed according to guideline OECD 401 with some minor variations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
, no constant volume at the different dose levels, partially shorter acclimatisation period than 5 days
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
3,5,5-trimethylhexanoic acid
EC Number:
221-975-0
EC Name:
3,5,5-trimethylhexanoic acid
Cas Number:
3302-10-1
Molecular formula:
C9H18O2
IUPAC Name:
3,5,5-trimethylhexanoic acid
Test material form:
liquid
Details on test material:
Name of test material (as cited in study report): Isononansäure
Charge 1144 from 1985-11-19, not specified isomer mixture, purity 99,7% with 0.25-0.3% main impurities

Test animals

Species:
rat
Strain:
other: Bor:WISW (SPF TNO)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation: 169,2 g (average)
- Fasting period before study: 16 h
- Housing: 1-5 animals per cage
- Diet: R10 Alleindiät für Ratten, Ssniff Spezialfutter, Soest, Germany, ad libitum
- Water: ad libitum)
- Acclimation period: 4-8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15-fold
- Photoperiod (hrs dark / hrs light): 12 h/12 h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
631, 794, 1000, 1250, 1580 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Animals were weighed at day 0, 1, 7 and 14
- Clinical symptoms were recorded up to 6 h following treatment and daily thereafter
- Dead animals were examined macroscopically
- Observation period: 14 days
Statistics:
LD50 values and 95% confidence intervals were calculated using a method of Litchfield and Wilcoxon (reference stated)

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 160 mg/kg bw
95% CL:
> 1 018 - < 1 322
Mortality:
631 mg/kg bw: 0/5 (males), 0/5 (females)
794 mg/kg bw: 0/5 (males), 0/5 (females)
1000 mg/kg bw: 1/5 (males), 2/5 (females)
1250 mg/kg bw: 1/5 (males), 5/5 (females)
1580 mg/kg bw: 5/5 (males), 5/5 (females)
Clinical signs:
15-30 min after dosage, the animals showed clinical signs of toxicity in form of ruffled fur, cowering, stagger, slight sedation and ataxia as well as prone position. Subsequently animals showed lacrimation, hypoactivity diarrhoea, laboured breathing, moderate to severe sedation and ataxia, gasping respiratory sounds, hypothermia, trembling and wide opened eyes. Surviving animals recovered completely after 48 h.

Animals with clinical signs of toxicity:
631 mg/kg bw: 5/5 (males), 5/5 (females)
794 mg/kg bw: 5/5 (males), 5/5 (females)
1000 mg/kg bw: 5/5 (males), 5/5 (females)
1250 mg/kg bw: 5/5 (males), 5/5 (females)
1580 mg/kg bw: 5/5 (males), 5/5 (females)
Body weight:
The body weight gain was not affected by the treatment.
Gross pathology:
Macroscopic examination of perished animals showed hyperemia of stomach and intestinal mucosa, scattered discolouration of liver and kidneys as well as extensively filled urinary bladders. Further observations were: hyperemia of the mucosa of the urinary bladder in 1 animal, hyperemia of the lung: 2 animals, hyperemia of the pancreas: 4 animals, hyperemia of the subcutis: 4 animals. Necroscopy of surviving animals at the end of the observation period revealed partially severe hyperemia of the small intestine mucosa.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of this study, all tested doses (single oral doses of 631 mg/kg bw and above) were toxic to rats and the LD50 was 1160 mg/kg bw.
Executive summary:

Single oral doses of > 631 mg/kg bw were toxic to fasted rats, producing clinical signs of toxicity and an increased mortality at doses of > 1000 mg/kg bw. The LD50 was 1160 (1018 -1322) mg/kg bw (Hüls AG, 1986).

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