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Description of key information

Two guinea pig studies of skin sensitisation are available for fenitrothion.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data (published article)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Maximisation
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Published literature study; performed prior to the adoption of OECD TG 429
Specific details on test material used for the study:
Fenitrothion: no additional details reported
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Route:
intradermal
Vehicle:
water
Concentration / amount:
5%
Day(s)/duration:
Not reported
Adequacy of induction:
not specified
Route:
other: dermal
Vehicle:
water
Concentration / amount:
25%
Day(s)/duration:
Not reported
Adequacy of induction:
not specified
No.:
#1
Route:
other: dermal
Vehicle:
water
Concentration / amount:
0.5%, 5%
Day(s)/duration:
Not reported
Adequacy of challenge:
not specified
No. of animals per dose:
10
Details on study design:
0.5% (challenge), 5% (intradermal induction and challenge) or 25% (dermal induction) fenitrothion in distilled water was applied. Induction and challenge were undertaken according to the original method. Skin reactions were observed 24 and 48 hours after removal of the patch, and the results were graded using a procedure by Kligman.
Challenge controls:
No data
Positive control substance(s):
not specified
Positive control results:
Not reported
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5%
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.5%
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Remarks on result:
not measured/tested
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Remarks on result:
not measured/tested
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Remarks on result:
not measured/tested
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Remarks on result:
not measured/tested

Summary of dermal reactions

Name

Challenge concentration

Response (%)

 

24h

48h

Fenitrothion

5%

70

70

 

0.5%

30

40

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
Based on the results of this study (sensitisation of >=30% in response to an intradermal induction of >1.0%), fenitrothion is considered to be a moderate sensitiser and is classified as a skin sensitiser in Category 1B according to the CLP Regulation.
Executive summary:

The skin sensitisation potential of fenitrothion was investigated in a published guinea pig Maximisation study. Groups of guinea pigs were induced using intradermal injection of 5% fenitrothion (in distilled water) and dermal application of 25% fenitrothion. All animals were subject to dermal challenge using 0.5% and 5% fenitrothion; dermal reactions were assessed at 24 and 48 hours following the challenge application. At 24 hours, positive responses were reported for 30% of the animals exposed to 0.5% fenitrothion and 70% of the animals exposed to 5% fenitrothion. At 48 hours, positive responses were reported for 40% of the animals exposed to 0.5% fenitrothion and 70% of the animals exposed to 5% fenitrothion. The study therefore indicates that fenitrothion is a skin sensitiser and requires classification as a skin sensitiser in Category 1B according to the CLP Regulation.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1 July 1972 - 20 August 1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to
Guideline:
other: Sacchuzai Shi-shin (Guideline for toxicity testing of insecticides for sanitary use, Japan) equivalent to Landsteiner-Draize’s method
Deviations:
no
GLP compliance:
no
Type of study:
other: Landsteiner-Draize method
Justification for non-LLNA method:
The study was performed prior to the development and adoption of the LLNA
Specific details on test material used for the study:
Fenitrothion
Batch No.: 417
Purity: 97.2%
Species:
guinea pig
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Nihon Dobutsu Co., Osaka
- Weight at study initiation: 250-300 g
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-27
- Humidity (%): 50-70
Route:
intradermal
Vehicle:
corn oil
Concentration / amount:
0.1 mL of a 1% or 5% solution
Day(s)/duration:
Ten injections, on alternate days
Adequacy of induction:
not specified
No.:
#1
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
0.05 mL by intradermal injection or 0.03 mL dermal application; 1% or 5% solution
Day(s)/duration:
Single exposure
Adequacy of challenge:
not specified
No. of animals per dose:
6
Details on study design:
0.1 ml of a 1% or 5% solution of fenitrothion in corn oil was injected intradermally to the back of animals, every other day for a total of 10 injections (except that 0.05 ml was used in the first sensitizing treatment). Two weeks after the last sensitizing injection, each animal was challenged by intradermal injection (0.05 ml) and dermal application (0.03 ml) of the same concentration as used for sensitizing injections. As a positive control, 0.1 ml of 0.05% DNCB (2,4-dinitrochlorobenzene) dissolved in corn oil was treated in the same way as fenitrothion, except that the sensitizing treatments were conducted 3 times every other day. The animals were challenged with 0.1% DNCB (intradermal injection), 0.3% (dermal application) and 1.0% (dermal application) as in the treated groups. Three negative control groups received corn oil as induction treatment. The animals were challenged with 5% fenitrothion (intradermal injection and dermal application), corn oil (intradermal injection), or DNCB (0.1%; intradermal injection, 1%; dermal application) as in the treated groups.
Challenge controls:
Corn oil
Positive control substance(s):
yes
Remarks:
DNCB
Positive control results:
In the animals sensitized and challenged with DNCB (intradermal injection or dermal application), haemorrhage and oedema were observed.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5%
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
DNCB, 1%
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
positive indication of skin sensitisation

Summary of dermal reactions

Group

A

B

C1

C2

C3

C4

D1

D2

D3

Induction:

Fenitrothion

Fenitrothion

Corn oil

DNCB

 

Challenge:

Fenitrothion

Fenitrothion

Corn oil

Fenitrothion

DNCB

 

DNCB

 

Concentration (%)

1

5

-

5

0.1

1

0.1

0.3

1

Number of animals used

6

6

3

3

3

3

5

5

5

Reactions

-

6/6

1/6

3/3

0/3

1/3

 

0/5

 

 

(intradermal

±

0/6

5/6

0/3

3/3

2/3

 

0/5

 

 

 injection)

+

0/6

0/6

0/3

0/3

0/3

 

3/5

 

 

 

++

0/6

0/6

0/3

0/3

0/3

 

2/5

 

 

 

+++

0/6

0/6

0/3

0/3

0/3

 

0/5

 

 

Reactions

-

6/6

6/6

 

3/3

 

3/3

 

0/5

0/5

(dermal

±

0/6

0/6

 

0/3

 

0/3

 

0/5

0/5

 application)

+

0/6

0/6

 

0/3

 

0/3

 

0/5

0/5

 

++

0/6

0/6

 

0/3

 

0/3

 

3/5

0/5

 

+++

0/6

0/6

 

0/3

 

0/3

 

2/5

5/5

-: No sign

±: Very slight swelling and erythema

+: Slight swelling and hyperaemia,

++: Moderate swelling and hyperaemia

+++: Severe swelling and hyperaemia

Interpretation of results:
GHS criteria not met
Conclusions:
There was no evidence of skin sensitisation in this study; fenitrothion is not therefore classified as a skin sensitiser on the basis of this study.
Executive summary:

The skin sensitisation potential of fenitrothion was investigated in a guinea-pig study following the Landsteiner-Draize method. 0.1 ml of a 1% or 5% solution of fenitrothion in corn oil was injected intradermally to the back of animals, every other day for a total of 10 injections (except that 0.05 ml was used in the first sensitizing treatment). Two weeks after the last sensitizing injection, each animal was challenged by intradermal injection (0.05 ml) and dermal application (0.03 ml) of the same concentration as used for sensitizing injections.  As a positive control, 0.1 ml of 0.05% DNCB (2,4-dinitrochlorobenzene) dissolved in corn oil was treated in the same way as fenitrothion, except that the sensitizing treatments were conducted 3 times every other day. The animals were challenged with 0.1% DNCB (intradermal injection), 0.3% (dermal application) and 1.0% (dermal application) as in the treated groups.  Three negative control groups received corn oil as induction treatment. The animals were challenged with 5% fenitrothion (intradermal injection and dermal application), corn oil (intradermal injection), or DNCB (0.1%; intradermal injection, 1%; dermal application) as in the treated groups. In the animals sensitized and challenged with DNCB (intradermal injection or dermal application), haemorrhage and oedema were observed. There was no evidence of skin sensitisation in this study. Findings of swelling and slight hyperaemia seen following intradermal challenge with 5% fenitrothion were considered to be due to primary irritation. Fenitrothion is not therefore classified as a skin sensitiser on the basis of this study.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

An older non-guideline study reports a negative result; a published Maximisation assay reports a positive result.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Fenitrothion has a harmonised classification under CLP and is not classified as a skin sensitiser. The results of the key (Maximisation) study indicates a potential for skin sensitisation; therefore classification for skin sensitisation is proposed for fenitrothion. Based on the results of the key study (sensitisation of >=30% in response to an intradermal induction of >1.0%), fenitrothion is considered to be a moderate sensitiser and is classified as a skin sensitiser in Category 1B according to the CLP Regulation.