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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study meets scientific standards with acceptable restrictions (dose-range-finding study; exposure period only 14 days; limited toxicological parameters studied, e.g. no haematology, clinical chemistry, histopathology; reliable concerning body weight and mortality)

Data source

Reference
Reference Type:
publication
Title:
Toxicology and carcinogenesis studies of 2-chloroethanol (ethylene chlorohydrin) in F344/N Rats and Swiss CD-1 Mice (dermal studies)
Author:
NTP
Year:
1985
Bibliographic source:
NTP TR 275; National Institutes of Health (USA), NIH Publication No.86-2531

Materials and methods

Principles of method if other than guideline:
Dose-range-finding study; toxic effects in a subacute dermal study in rats
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Kodak Co. (lot no. A3X)
identified by infrared spectroscopy and nuclear magnetic resonance spectroscopy
purity >99%
stored in the dark at 5 C; no degradation (analysis)
solution in water stable for more than 21 days

Test animals

Species:
rat
Strain:
other: F344/N
Sex:
male/female
Details on test animals and environmental conditions:
Source: Charles River Breeding Laboratories (Portage, Ml; USA)
- Acclimatisation: 4 weeks
- Age at study initiation: 8 wk
- mean weight at study initiation: males 173-181 g; females 128-137 g
- Fasting period before study: no data
- Housing: rats housed 5 per cage
- Diet (Purina Lab Chow) ad libitum
- Water (Tap water acidified to pH 2.5 by HCl) ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
open
Vehicle:
other: ethanol/water, 80/20
Details on exposure:
Route of Administration: dermal
TEST SITE
- Area of exposure: interscapular region, hair clipped (6 cm x 6 cm);
- clipplings 2 times per week
- Application volume: 0.1 ml
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
14 days
Frequency of treatment:
once daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 20, 30, 40, 60, 80 mg/rat
Basis:
other: nominal per rat
Remarks:
Doses / Concentrations:
0/0, 114/147, 172/222, 226/313, 339/451, 442/611 mg/kg bw (males/females)
Basis:
nominal per unit body weight
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: no
Positive control:
no

Examinations

Observations and examinations performed and frequency:
clinical signs recorded 2-times per day
Body weight measured at day 0, 7, and 14
Sacrifice and pathology:
Necropsy performed
Other examinations:
no
Statistics:
no data

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Dermal irritation:
not specified
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
Mortality: 2/5 females at 60 mg/rat (but all other female rats including high dose females survived) and 1/5 males at 80 mg/rat.
Body weight gain: no effects detectable.
No data given on clinical signs or necropsy in the result section.

Effect levels

Dose descriptor:
NOEL
Effect level:
40 other: mg/rat
Sex:
male/female
Basis for effect level:
other: related to mortality and bdy weight

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Dose-range-finding study for the subsequent 13 -week study.

Applicant's summary and conclusion

Conclusions:
In rats dermal exposure to doses up to 40 mg/rat once daily (226/313 mg/kg bw/day in males/females) for 14 days has no effects on body weight or survival.
Executive summary:

The study meets scientific standards with acceptable restrictions (dose-range-finding study; exposure period only 14 days; limited toxicological parameters studied, e.g. no haematology, clinical chemistry, histopathology; reliable concerning body weight and mortality).

Five male and 5 female F344/N rats were dermally exposed once daily to 0, 20, 30, 40, 60, 80 mg/rat (corresponding to 0/0, 114/147, 172/222, 226/313, 339/451, 442/611 mg/kg bw in males/females) for 14 days. Mortality occurred in 2/5 females at 60 mg/rat (but all other female rats including high dose females survived) and 1/5 males at 80 mg/rat. No effects were reported on body weight gain.

Conclusion: In rats dermal exposure to doses up to 40 mg/rat once daily (226/313 mg/kg bw/day in males/females) for 14 days has no effects on body weight or survival.