Cyclohexyldimethylammonium dihydrogen phosphate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

8th January 1986 to 30th January 1986.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study, not GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Details on test material:

Polycat 8CAS 98-94-2 (cyclohexyldimethylamine), N,N-dimethylcyclohexylamine (DMCHA)purity not indicated Lot # 79-507-CJLiquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: Interfauna U.K. Limited, Wyton, Huntingdon.- Age at study initiation: ten to fourteen weeks old. - Weight at study initiation: Males: 200 - 254g Females: 200 - 245g- Fasting period before study: Not documented- Housing: Housed in polypropylene cages with sawdust bedding.- Diet (e.g. ad libitum): Rat and Mouse Expanded Diet No. 1 ad libitum- Water (e.g. ad libitum): Mains drinking water ad libitum- Acclimation period: Not documentedENVIRONMENTAL CONDITIONS- Temperature (°C): 19 - 22°C- Humidity (%): 45 - 60%- Air changes (per hr): Approximately 15 changes per hour- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours darkIN-LIFE DATES: From: 8 January 1986 To: 30 January 1986

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE- Area of exposure: Back and flanks of each animal, approximately 6 x 12 cm.- % coverage: Approximately 10%- Type of wrap if used: A sheet of aluminium foil (7 x 4cm) was placed over the treatment area and occluded with a double layer of adhesive strapping (SLEEK) wrapped around the trunk of the rat.REMOVAL OF TEST SUBSTANCE- Washing (if done): Yes - the test area and surrounding hair were wiped with moist absorbant paper to remove any residual test sample. - Time after start of exposure: After the 24 hour contact periodTEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.36, 0.43, 0.50 and 0.59 ml/kg.

Duration of exposure:

24 hours

Doses:

300, 360, 420, 500 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

EXAMINATIONS: 14 days observation period mortality/clinical signs 1 and 4 hours after dosing and once daily thereafter body weights prior to dosing and on day 7 and 14 macroscopy on all animals.

Statistics:

Weil C.S. (1952), Biometrics 8, 249

Results and discussion

Preliminary study:

Not relevant

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

380 mg/kg bw

Based on:

not specified

95% CL:

330 - 440

Remarks on result:

other: Three animals (1 male and 2 females) were found dead at the 4 hour observation and one male and female were found dead on day 1.

Mortality:

- Time of death: all within 1 day post-dose   dose male  female  all 300   2/5    0/5   2/10 360   2/5    3/5   5/10 420   2/5    4/5   6/10 500   3/5    5/5   8/10

Clinical signs:

(a) during exposure: in majority hunched posture, pilo-erection, lethargy, ataxia, decreased respiratory rate or gasping respiration, ptosis, tail arching, (occasional) body tremors. In minority red/brown staining around the eyes and/or nose, tail lashing, increased salivation and/or lacrimation. Incidental tiptoe gait (420 and 360 mg/kg), tonic or clonic convulsions, loss of righting reflex (420 mg/kg) and exophthalmos (300 mg/kg). (b) post-exposure: hunched posture, pilo-erection, lethargy, decreased respiratory rate, ataxia. Symptoms disappeared 2-3 days after treatment.

Body weight:

No treatment-related effect

Gross pathology:

(a)in animals that died: congested lungs at 360 and 420 mg/kg. Haemorrhage of the subcutis, dark staining or reddening of the treatment site at all doses in all animals dying during the study. In some of these animals the upper layer of skin was peeling away from the underneath skin.(b) in survivors: eschar on the application site with dark areas below eschar formation

Other findings:

No additional results

Any other information on results incl. tables

In the preliminary range finding study, the mortalities recorded indicated a dermal LD50 in the range of 500 - 1000 mg/kg. However, mortalities were apparent soon after dosing the initially selected low dose group (500 mg/kg) and the selected dose levels were revised, making the 500 mg/kg the high dose group.

No additional findings were noted in the main test group.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Under the conditions of the study, the dermal LD50 of DMCHA was determined to be 380 mg/kg (330 - 440 mg/kg 95% confidence limits). Based on these results, the test substance should be classified as a Category 3 acute dermal toxicant according to Regulation EC No. 1272/2008 and should have the signal word Danger and the hazard statement H301: Toxic if swallowed associated with it. In accordance with Directive 67/548/EEC, the test substance should be classified as Toxic (T) and have the risk phrase R24 Toxic in contact with skin associated with it.

Executive summary:

In a study conducted by Jones and Collier (1986), the test substance, cyclohexyldimethylamine (DMCHA), was examined for its ability to cause acute dermal toxicity when applied to the backs and flanks of male and female Sprague-Dawley rats. A preliminary study was performed to determine the appropriate dose level to use, with 300, 360, 420 and 500 mg/kg being selected as the dose concentrations to use in the main study. The test substance was applied under an occlusive dressing and left in place for 24 hours. Following the 24 hour contact period, the dressing was removed and the test site and surrounding hair was washed with moist absorbent paper to remove any remaining test substance. Deaths were dose related with 2 deaths at 300 mg/kg, 5 deaths at 360 mg/kg, 6 deaths at 420 mg/kg and 8 deaths at 500 mg/kg. All deaths occurred within the first 24 hours and survivors all appeared normal after 3 days, with the exception of skin damage at the treatment site. Signs of toxicity included ataxia, tremors, tail arching and convulsions. At necropsy after 14 days, survivors showed no abnormalities of internal organs but all showed extensive skin damage. Under the conditions of the study, the dermal LD₅₀ of DMCHA was determined to be 380 mg/kg (330 - 440 mg/kg 95% confidence limits). Based on these results, the test substance should be classified as a Category 3 acute dermal toxicant according to Regulation EC No. 1272/2008 and should have the signal word Danger and the hazard statement H311: Toxic in contact with skin

associated with it. In accordance with Directive 67/548/EEC, the test substance should be classified as Toxic (T) and have the risk phrase R24 Toxic in contact with skin associated with it.