1-chloro-N,N-diethyl-1,1-diphenyl-1-(phenylmethyl)phosphoramine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From May 1983 to October 1983.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Several animals died or had to be sacrificed after the induction in the main study with no clear evidence that the mortality was treatment related. The remaining number of animals in the treated group at challenge is still compliant with acceptability current standards. Only one reading was done, at 24 hrs after challenge.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Magnusson and Kligman

GLP compliance:

no

Remarks:

prior to GLP guidelines

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

GM102E

IUPAC Name:

GM102E

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C):20 °C +/- 3
- Humidity (%): monitored
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: To:

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: distilled water

Induction 2

Concentration / amount:

Concentration of test material and vehicle used at induction:
- intradermal: 1% (v/v)
- epicutaneous: 50 % (v/v)
Concentration of test material and vehicle used for each challenge: 50 % (v/v)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: distilled water

Challenge 2

Concentration / amount:

Concentration of test material and vehicle used at induction:
- intradermal: 1% (v/v)
- epicutaneous: 50 % (v/v)
Concentration of test material and vehicle used for each challenge: 50 % (v/v)

No. of animals per dose:

Number of animals in test group: 20
Number of animals in negative control group: 20

Details on study design:

RANGE FINDING TESTS:
intradermal injection: 10, 5, 2, 1% (v/v) in distilled water
epicutanous application: 50% (w/w) in distilled water. No Sodium lauryl sulfate pre-treatment was necessary.
doses for challenge: 50, 25, 10 and 5 % (w/w) in distilled water, occlusive application.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal injection (1%) and 1 epicutaneous occlusive application (50%)
- Exposure period: 48 hours for the epicutaneous induction
- Concentrations: intradermal injection (1%) ; epicutaneous occlusive application (50%)

B. CHALLENGE EXPOSURE
- No. of exposures: 1 epicutaneous exposure
- Exposure period: 24 hours occlusive application
- Concentrations: 50% (w/w)
- Evaluation (hr after challenge): 24 hours

Challenge controls:

The control group (20 guinea-pigs) was treated similarly to the treated group, except the test material was replaced by distilled water.
A group of 10 guinea-pigs was treated with a positive control (DNCB: injection 0.1% (w/w) in propyleneglycol, topical induction: 1% (w/w) in propylene glycol, challenge: 0.05 and 0.025% (w/w) in propyleneglycol).

Positive control substance(s):

yes

Remarks:

Dinitrochlorobenzene (DNCB)

Results and discussion

Positive control results:

Positive controls produced the expected response: 10/10 reacted to 0.05% and 5/10 reacted to 0.025%.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

10 out of 20 were actually challenged due to mortality and infection after the topical induction period

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: 10 out of 20 were actually challenged due to mortality and infection after the topical induction period.

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0 %

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0 %. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

Maximum concentration not causing irritating effects in preliminary test: 50 %

Signs of irritation during induction: none

Evidence of sensitisation of each challenge concentration: None

Other observations:
5 test group animals were found dead 24 hours after the topical induction application of the compound and 1 was sacrificed due to very poor conditions.

There was no conclusive evidence from histopathological examinations that the test material was responsible for the deaths. There was no indications of infectious disease.

4 test group animals were sacrificed before challenge due to infected injection sites.

Thus, 10 surviving test group animals were submitted to challenge application.

Only one reading is described in the study report (at 24 hours).

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information not classified Criteria used for interpretation of results: EU

Conclusions:

There was no evidence of skin sensitising reactions in the 10 treated animals that survived challenge application.

Executive summary:

The sensitizing potential of the test item GM102E was investigated in a test performed on female Dunkin-Hartley guinea pigs according to the Magnusson and Kligman method. 

The test item was applied respectively at 1% (v/v) and 50% (v/v) in distilled water by intradermal and epicutaneous route for the induction exposure while epicutaneous route (occlusive) was used for the challenge exposure with a concentration of 50% (v/v) of test item. Those doses were decided after a range finding test.

For the test, 20 animals were used in the test group and another 20 guinea pigs were used in a control group. The lab provided background positive control data.

Positive controls produced the expected response: 10/10 reacted to 0.05% and 5/10 reacted to 0.025%.

Five test group animals were found dead 24 hours after the topical induction application of the compound and one was sacrificed due to very poor conditions. There was no conclusive evidence from histopathological examinations that the test material was responsible for the deaths. There was no indication of infectious disease. Four test group animals were sacrificed before challenge due to infected injection sites. 

Thus, 10 surviving test group animals were submitted to challenge application. None of these animals reacted positively to this topical application.

Based on these results and according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP), GM102E should not be classified for sensitization.