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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP status not known, guideline study, published in peer reviewed literature, no restrictions, fully adequate for assessment.

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
60.2% m-xylene, 13.6% p-xylene, 9.1% o-xylene, and 17.0% ethylbenzene

Test animals

Species:
rat
Strain:
other: F344/N
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories (Kingston, NY, USA)
- Age at study initiation: 7 weeks
- Housing: 5 per sex /cage in polycarbonate cages
- Diet: Purina Lab Chow available ad libitum
- Water: ad libitum
- Acclimation period: 18 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22° ± 1°C
- Humidity: 40 - 60%
- Air changes: 15 air changes/hour
- Photoperiod: 12 hour dark/ 12 hour light

IN-LIFE DATES: From: 5 March 1979 To: 19 March 1979

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Oral (gavage): 500, 1000, 2000, 4000 or 6000 mg/kg xylenes (mixed) in corn oil; dose volume 8 mL/kg
Preparation: Weighed portions of xylenes (mixed) were placed in a graduated cylinder and mixed with corn oil.
Doses:
Single dose
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Groups of five rats of each sex were administered a single dose of 500, 1,000, 2,000, 4,000, or 6,000 mg/kg xylenes in corn oil by gavage. The animals were observed twice daily for 14 days and were killed on day 16. A necropsy was not performed.
Statistics:
LD50 calculated by Spearman-Karber procedure.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
3 523 mg/kg bw
95% CL:
2 707 - 4 587
Sex:
female
Dose descriptor:
LD50
Effect level:
> 4 000 mg/kg bw
Mortality:
All the rats that received 6,000 mg/kg and 3 of 5 males that received 4,000 mg/kg died within 48 hours of dosing.
Clinical signs:
Lack of coordination, prostration, loss of hindleg movement, and hunched posture were detected within 24 hours of dosing in male and female rats that received 4,000 or 6,000 mg/kg.
Male and female rats that received 2,000 mg/kg had rough coats.
No clinical signs of toxicity were noted in the surviving animals at the end of week 1.
Body weight:
Body weight gain was decreased in the higher dose groups.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 in rats was 3523 mg/kg/bw for males and greater than 4000 mg/kg/bw for females.
Executive summary:

In a single-administration study, groups of five F344/N rats of each sex received 500, 1,000, 2,000, 4,000, or 6,000 mg/kg. Administration of mixed xylenes caused deaths at 6,000 mg/kg in each sex and at 4,000 mg/kg in males. Clinical signs observed within 24 hours of dosing at 4,000 mg/kg included prostration, muscular incoordination, and loss of hind limb movement; these effects continued through the second week of observation. The LD50 was 3523 mg/kg/bw for males and greater than 4000 mg/kg/bw for females.