Reaction product of propargyl chloride and sodium bisulfite

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 27, 2017-March 14, 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

February 24, 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

30 May 2008

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147

Version / remarks:

November 24, 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bioassay Labor für biologische Analytik GmbH, 69120 Heidelberg, Germany

Test type:

fixed dose procedure

Limit test:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: CA AQ02372
- Expiration date of the lot/batch: June 17, 2018

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: The stability of the test item under storage conditions over the study period was guaranteed by the sponsor.

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: 232.4 ± 5.2 g (male) and 201.2 ± 8.07 g (female)
- Fasting period before study: no
- Housing: Makrolon cage, type III, single housing
- Bedding: H 15005-29; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany)
- Enrichment: Wooden gnawing blocks (Type NGM E-022) ; ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria
- Diet: ad libitum, VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: ad libitum, tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): approx.10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: about 40 cm²
- % coverage: corresponds to at least 10% of the body surface
- Type of wrap if used: covering of the application site with a semi-occlusive dressing [air-permeable dressing;4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG] for 24 hours

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 13.24 mL/kg bw
- Concentration (if solution): undiluted
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

15773 mg/kg bw (The applied dose was adjusted regarding to the purity of the test item of approx. 31.7 % to ensure an actual dose of 5000 mg/kg bw.)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation.
Clinical signs for each animal were recorded several times on the day of application and at least once during each workday thereafter. Scoring of skin findings30-60 min after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation. A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes, necropsy with gross-pathology examination was performed on the last day of the observation period
- Other examinations performed: clinical signs, body weight, histopathology

The evaluation of skin reactions was performed according to Draize, J. H. "Dermal toxicity."
Erythema and eschar formation:

0 No erythema
1 Very slight erythema (barely perceptible)
2 Well- defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) to eschar formation preventing grading of erythema

Edema formation

0 No edema
1 Very slight edema (barely perceptible)
2 Slight edema (edges of area well- defined by definite raising)
3 Moderate edema (raised approx. 1 mm)
4 Severe edema (raised more than 1 mm and extending beyond area of exposure)

Statistics:

Calculations were performed using Microsoft Excel 2010 and checked with a calculator.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

No systemic clinical signs were observed during clinical examination. No local effects were observed.

Body weight:

The body weight of all animals increased within the normal range throughout the study period.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals.

Any other information on results incl. tables

Analysis of feed:

In view of the aim and duration of the study, the contaminants occurring in commercial feed should not influence the results.

Analysis of drinking water: In view of the aim and duration of the study, there are no special requirements exceeding the specification of drinking water.

Analysis of bedding and enrichment:

In view of the aim and duration of the study, there are no special requirements exceeding the specification of a commercial grade monitored by the manufacturer.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met