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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1990/10/22-1990/11/06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to OECD 420 guideline. GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Hydrocarbons, C10-C13, aromatics, >1% naphthalene
EC Number:
926-273-4
IUPAC Name:
Hydrocarbons, C10-C13, aromatics, >1% naphthalene

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan
- Age at study initiation: Approximately 9 - 10 weeks
- Weight at study initiation: Males (260-295 g), Females (201-228 g)
- Fasting period before study: approximately 16h
- Housing: individual
- Diet (e.g. ad libitum): Purina certified rodent chow, ad libitum
- Water (e.g. ad libitum): Automatic watering system, ad libitum
- Acclimation period: 7d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The test material MRD-90-884 was diluted in corn oil and administered at the appropriate dose levels by a single oral intubation via syringe and a no. 16 stainless steel straight, ball-tipped feeding needle.
Doses:
500 mg/kg, 1500 mg/kg, 5000 mg/kg
No. of animals per sex per dose:
Male (5), Female (5); total animals (30)
Control animals:
no
Details on study design:
Duration of observation period following administration: 1, 2, 4, and 6 h after dosing and once per day thereafter for a total of 14 days
Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The means and standard deviations of the body weights and body weight changes were calculated. LD50 was calculated using the standard Litchfield-Wilcoxon technique with equal weighting of the data points.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
10 650 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
5 210 mg/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
7 050 mg/kg bw
Remarks on result:
other: combined LD50
Mortality:
No mortality was observed in the 500 or 1500 mg/kg doses. In the 5000 mg/kg dose group, two males were found dead on day 2; two females were found dead on day 3, and a final female death noted on day 4.
Clinical signs:
No abnormal clinical in-life observations were noted for the majority of animals in either the 500 or 1500 mg/kg doses; only a single incidence ano-genital staining and a single oral/ocular discharge were noted. In the 5000 mg/kg group the most frequently noted abnormalities were ano-genital staining, oral/nasal discharges, small amount of soft stool, decreased appetite, emaciation, hypoactivity, and prostration.
Body weight:
All surviving animals showed an increase in body weight over their initial values at the end of the observation period.
Gross pathology:
No abnormal pathological observations were noted for the animals in either the 500 or 1500 mg/kg dosed groups. The animals that succumbed prior to study termination exhibited staining of the lungs and of the fur, abnormalities of the stomach and gastro-intestinal tract, liver discoloration and distension, and abnormal contents of the cecum and urinary bladder. Four of the five survivors in this group displayed no abnormalities, while the remaining animals exhibited alopecia.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 for males is 10650 mg/kg and the LD50 for female animals is 5210 mg/kg. The combined estimated LD50 (both sexes) is 7050mg/kg. This finding does not warrant classification as an acute oral toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations
Executive summary:

The acute toxicity of MRD-90-884 was evaluated in rats via oral gavage at doses of 500 mg/kg, 1500 mg/kg, or 5000 mg/kg fasted body weight. Observations were made as to the nature, onset, severity, and duration of toxicological signs at 1, 2, 4, and 6 hours after dosing and once per day for a total of 14 days. Animals in the 500 or 1500 mg/kg dose groups survived the entire observational period and displayed a low incidence of clinical symptoms. Two males and three female animals in the 5000 mg/kg dosing group did not survive the study and died on days 2 - 4. The most frequently noted in-life clinical abnormalities were ano-genital staining, oral/nasal discharges, decreased appetite, hypoactivity, and prostration. Gross postmortem examination of the animals that succumbed prior to study termination revealed staining of the lungs and of the fur, and abnormalities of the stomach, gastro-intestinal tract, liver and bladder.  The surviving animals displayed little or no abnormalities. The surviving animals had no observable abnormalities. It is estimated that the LD50 for males is 10650 mg/kg and the LD50 for female animals is 5210 mg/kg. The combined estimated LD50 (both sexes) is 7050mg/kg. This finding does not warrant classification as an acute oral toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations