2-chloro-1,1-dimethoxyethane

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to OECD Guideline Study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethane, 2-Chloro-1,1-Dimethoxy-

IUPAC Name:

Ethane, 2-Chloro-1,1-Dimethoxy-

Constituent 2

Reference substance name:

97-97-02

IUPAC Name:

97-97-02

Constituent 3

Reference substance name:

2-chloro-1,1-dimethoxyethane

EC Number:

202-624-0

EC Name:

2-chloro-1,1-dimethoxyethane

Cas Number:

97-97-2

Molecular formula:

C4H9ClO2

IUPAC Name:

2-chloro-1,1-dimethoxyethane

Test material form:

other: colourless liquid

Details on test material:

- Name of test material (as cited in study report): Chloroacetaldehyde dimethylacetal
- Physical state: colourless liquid
- Storage condition of test material: room temperature
- Container: brown glass bottle x2

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (U.K.) Limited, Manston, Kent
- Age at study initiation: 5-6 weeks
- Weight at study initiation: males: 137-168g, females: 127-159g
- Housing: polypropylene grid-floor cages suspended over trays lined with absorbent paper
- Diet: free access to food except during urine collection when food was withdrawn overnight
- Water: free access
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22°C
- Humidity (%): 37-68%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0 (control), 15.3, 51, 204, 0 (satellite), 204 (satellite) mg/kg/day
Basis:
nominal in diet

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

yes, concurrent vehicle

yes, plain diet

Examinations

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: immediately before dosing and one and five hours after dosing during working week; immediately before dosing and one hours after dosing at weekends and public holidays; twice daily, morning and afternoon during treatment free period (one daily at weekends).

BODY WEIGHT: Yes
- Time schedule for examinations: day 0, 7, 14, 21, 28

FOOD&WATER CONSUMPTION: Yes

HAEMATOLOGY: Yes
- Time schedule for collection of blood: end of study (day 28)
- Anaesthetic used for blood collection: Yes: Clotting time was assessed by "Hepato Quick" time using samples collected into sodium citrate solution (0.11 mol/L)
- Animals fasted: Yes
- How many animals: all from groups 1-4

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: end of study (day 28)
- Animals fasted: No
- How many animals: all of groups 1-4

URINALYSIS: Yes
- Time schedule for collection of urine: collected over a period of approx. 16h
- Parameters were examined:Volume, Specific gravity, pH, Protein, Glucose, Ketones, Bilirubin, Urobilinogen, Reducing substances, Blood
- animals: all
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes but normal hydration

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

no effects observed

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

changes in kidney weights, liver weights

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

changes in kidneys, not relevant for humans

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

The administration of CADMA by oral gavage for a period of twenty-eight con-secutive days resulted in toxicologically significant changes at dose levels of 50 and 200 mg/kg/day. Increases in plasma alkaline phosphatase and bilirubin were apparent, although statistical significance was not achieved, possibly suggesting a slight liver change. This was supported by increases in liver weight in both sexes, however there were no histopathological changes. Kidney weights were also ele-vated in animals of both sexes treated with 200 mg/kg/day. Microscopic examina-tion of kidney sections revealed intracytoplasmic hyaline droplet formation in the proximaltubular epithelium of male rats treated with 50 and 200 mg/kg/day. These changes resemble a well documented (Alden C.L. (1986). A Review of Unique Male Rat Hydrocarbon Nephropathy. Toxicologic Pathology 14.1. pp. 109-111) hydrocarbon nephropathy which occurs in male rats but not in other species. This effect is therefore not indicative of a hazard to human health. Nevertheless, statisti-cally significant increases in kidney weight were also detected in females treated with 200 mg/kg/day and it is therefore possible that another slight renal change was also present in high dose animals.

Effect levels

Dose descriptor:

NOAEL

Effect level:

50 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Organ weights, clinical chemistry

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Oral administration of the test material Chloroacetaldehyde dimethylacetal, to rats for a period of 28 consecutive days at dose levels of up to 200 mg/kg/day resulted in toxicologically significant changes at 50 and 200 mg/kg/day.
The NOEL is, therefore, considered to be 15 mg/kg/day. However, the changes at 50 mg/kg/day were confined to a kidney effect resembling hydrocarbon nephropathy which only occurs in male rats and is, therefore, not indicative of a hazard to human health.

Executive summary:

The test material Chloroacetaldehyde dimethylacetal was administered by gavage to three groups, each of five male and five female Sprague-Dawley CD strain rats, for 28 consecutive days, at dose levels of 15, 50 and 200 mg/kg/day (incorporating a correction factors to allow for 98% purity) comparable to the OECD Guideline Study 407. A control group of five males and five females was dosed with vehicle alone (arachis oil B.P.). Two satellite groups, each of five males and five females were treated with the high dose (200 mg/kg/day) or the vehicle alone throughout the 28 day study period and then maintained without treatment for a further 14 days.

Clinical signs, bodyweights, food and water consumptions were monitored during the study. Haematology, blood chemistry and urinalysis were evaluated for all main group animals during the final week of dosing. Parameters showing possible abnormalities were examined in satellite group animals at the end of the treatment-free period. All animals were subjected to a gross necropsy examination with histopathological evaluation of selected tissues.

Oral administration of the test material Chloroacetaldehyde dimethylacetal, to rats for a period of 28 consecutive days at dose levels of up to 200 mg/kg/day resulted in toxicologically significant changes at 50 and 200 mg/kg/day.

The NOEL is, therefore, considered to be 15 mg/kg/day. However, the changes at 50 mg/kg/day were confined to a kidney effect resembling hydrocarbon nephropathy which only occurs in male rats and is, therefore, not indicative of a hazard to human health.. The NOAEL therefore is 50 mg/kg bw.