2-chloroethanol

Repeated dose toxicity: dermal

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

Test material information

Constituent 1

Reference substance name:

2-chloroethanol

EC Number:

203-459-7

EC Name:

2-chloroethanol

Cas Number:

107-07-3

Molecular formula:

C2H5ClO

IUPAC Name:

2-chloroethan-1-ol

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 or test system 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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 20, 30, 40, 60, 80 mg/rat
Basis:
other: nominal per rat

Doses / concentrations 2

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.