Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Four groups, each of 5 male and 5 female rats, administered a single oral dose, by gavage. Animals assessed for 7 days after which survivors were killed and subjected to necropsy examination.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Zucht Winkelmann, Paderborn, Germany
- Weight at study initiation: 120 - 145 g
- Fasting period before study: Yes - 16 hours
- Diet (e.g. ad libitum): Rodent diet, ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 deg C
- Humidity (%): 45 - 55%
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20%
- Amount of vehicle (if gavage): 12.5 - 24.8 mL/kg body weight
- Justification for choice of vehicle: Substance unstable in aqueous media

MAXIMUM DOSE VOLUME APPLIED: 24.8 mL/kg body weight
Doses:
2520, 3180, 3980 and 5000 mg/kg
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Examination 2, 24 and 48 hours post-dose and again after 7 days. Weighing on day of dosing and again after 7 days
- Necropsy of survivors performed: Yes
Statistics:
Litchfield and Wilcoxon

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 040 mg/kg bw
Based on:
test mat.
95% CL:
3 580 - 4 570
Mortality:
Dose level [mg/kg] - 2520; Males 0% Females 0%
- 3180: Males 20% Females 20%
- 3980: Males 40% Females 40%
- 5000: Males 100% Females 100%
Clinical signs:
Reduced activity, piloerection and ataxia observed following dosing and for at least 24 hours.
Body weight:
Changes in body weight were unremarkable
Gross pathology:
No notable findings in surviving animals

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Acute oral toxicity (LD50) of hexahydrophthalic anhydride is 4040 mg/kg body weight
Executive summary:

Acute oral toxicity following administration of a single dose has been investigated in the rat according to FHSA test methods. The median lethal dose (LD50) of hexahydrophthalic anhydride was determined to be 4040 mg/kg body weight.