Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 249-528-5 | CAS number: 29232-93-7
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 10 Jun 1999 to 17 Jul 1999
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 1999
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- 1992
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Version / remarks:
- 1996
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- Qualifier:
- according to guideline
- Guideline:
- other: Agricultural Chemicals Laws and Regulations, Japan (II). Dermal Sensitization Study, 27-29. Pub. Society of Agricultural Chemical Industry
- Version / remarks:
- 1985
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- Currently no LLNA study is available for assessment. The GPMT test has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD
Test material
- Reference substance name:
- Pirimiphos-methyl
- EC Number:
- 249-528-5
- EC Name:
- Pirimiphos-methyl
- Cas Number:
- 29232-93-7
- Molecular formula:
- C11H20N3O3PS
- IUPAC Name:
- O-2-(diethylamino)-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate
Constituent 1
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Remarks:
- Albino
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Age at study initiation: Young adults
- Weight at study initiation: 356-532 g
- Housing: The guinea pigs were housed five per cage in cages suitable for animals of this strain and the weight range expected during the course of the study.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15 changes
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: From: 10 Jun 1999 To: 17 Jul 1999
Study design: in vivo (non-LLNA)
Inductionopen allclose all
- Route:
- intradermal
- Vehicle:
- corn oil
- Concentration / amount:
- Injection: 0.05 - 0.1 mL
Treatment and control: Freund's Complete Adjuvant plus corn oil 1:1 - Day(s)/duration:
- Day 0: First injection out of the three pairs of intradermal injections
- Route:
- intradermal
- Vehicle:
- corn oil
- Concentration / amount:
- Injection: 0.05 - 0.1 mL
Treatment: 10% w/v of the test substance in corn oil
Control: Corn oil only - Day(s)/duration:
- Day 0: Second injection out of the three pairs of intradermal injections
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
- Route:
- intradermal
- Vehicle:
- corn oil
- Concentration / amount:
- Injection: 0.05 - 0.1 mL
Treatment: 10% w/v of the test substance in a 1:1 preparation of Freund's Complete Adjuvant plus corn oil
Control: Freund's Complete Adjuvant plus corn oil 1:1 - Day(s)/duration:
- Day 0: Third injection out of the three pairs of intradermal injections
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
- Route:
- epicutaneous, occlusive
- Vehicle:
- corn oil
- Concentration / amount:
- Patch: Occlusive dressing
Treatment: Application of the test substance 50% w/v in corn oil. This preparation (0.2-0.3 mL) was applied on filter paper (approximate size 4 cm x x2 cm)
Control: Corn oil only - Day(s)/duration:
- Day 7: Occlusive dressing for 48 hours
- Adequacy of induction:
- highest technically applicable concentration used
Challenge
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- corn oil
- Concentration / amount:
- A 50% w/v preparation of the test substance in corn oil (0.05-0. 1 mL) was applied to one of the pieces of filter paper and a 25% w/v preparation in corn oil (0.05-0.1 mL) was applied to the second piece of filter paper. Corn oil alone (0.05-0.1 mL) was applied to the third piece of filter paper. The dressing was placed on the shorn flank of the guinea pig so that the 50% w/v
preparation was on the top left, the 25% w/v preparation was on the bottom left and corn oil alone was on the top right. - Day(s)/duration:
- Day 20: Occlusive dressing for 24 hours
- Adequacy of challenge:
- highest non-irritant concentration
- No. of animals per dose:
- 20 test and 20 control animals
- Details on study design:
- MAIN STUDY
A. INDUCTION EXPOSURE
- Exposure period: 48 hours
- Test groups:
a) Top: Freund's Complete Adjuvant + corn oil in the ratio 1:1
b) Middle: 10% w/v of the test substance in corn oil
c) Bottom: 10% w/v of the test substance (1:1) in Freund's Complete Adjuvant
- Control group: Control animals were treated the same as the test animals, except that they were treated with corn oil in place of the test substance.
Day 6 INDUCTION: The scapular area was clipped again and 1 day later was treated with a topical application of the test substance as a 50% w/v preparation in corn oil. This was applied on filter paper (approximate size 4 cm x 2 cm)
- Duration: 8 days
- Concentrations: The test substance was dosed as a 10% w/v preparation in corn oil for the intradermal injections and was applied as a 50% w/v preparation in corn oil for the topical application
B. CHALLENGE EXPOSURE
- Exposure period: 24 hours
- Site: The shorn flank
- Concentrations: The test substance was applied as 50% or 25% w/v preparations in corn oil. The animals were also challenged with corn oil alone.
- Evaluation: Skin sites were examined approximately 1 and 2 days after removal of the dressings
OTHER:
Clinical observations: Prior to the start of the study, all guinea pigs were examined to ensure that they were physically normal and exhibited normal activity. Throughout the study, the animals were observed daily.
Body weight: The animals were weighed on the day before dosing (day -1) and at the end of the study. - Challenge controls:
- Corn oil
- Positive control substance(s):
- yes
- Remarks:
- Hexylcinnamaldehyde
Results and discussion
- Positive control results:
- There was no erythematous response in any of the control animals. The net percentage response was calculated to be 100% and, under the conditions of the test, hexylcinnamaldehyde was classified as an extreme skin sensitiser.
In vivo (non-LLNA)
Resultsopen allclose all
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 50% w/v in corn oil
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- None
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 50 w/v in corn oil
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- None
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 50% w/v in corn oil
- No. with + reactions:
- 2
- Total no. in group:
- 20
- Clinical observations:
- Scattered mild redness or moderate and diffuse redness
- Reading:
- 2nd reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 25% w/v in corn oil
- No. with + reactions:
- 2
- Total no. in group:
- 20
- Clinical observations:
- Scattered mild redness
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- 10% in paraffin wax
- No. with + reactions:
- 19
- Total no. in group:
- 19
- Remarks on result:
- positive indication of skin sensitisation
Any other information on results incl. tables
Table 1. Challenge responses (test group)
|
Test substance 50% w/v |
Test substance 25% w/v |
Test substance Corn oil |
|||||
|
Top |
Left |
Bottom |
Left |
Top |
Right |
||
Animal |
Sex |
24HRS |
48HRS |
24HRS |
48HRS |
24HRS |
48HRS |
|
61 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
62 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
63 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
64 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
65 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
66 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
67 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
68 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
69 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
70 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
71 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
72 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
73 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
74 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
75 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
76 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
77 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
78 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
79 |
F |
1 |
1 |
1 |
1 |
0 |
0 |
|
80 |
F |
1 |
2 |
1 |
1 |
0 |
0 |
|
Table 2. Challenge response (control group)
|
Test substance |
Test substance |
Test substance Corn oil |
|||||
|
Top |
Left |
Bottom |
Left |
Top |
Right |
||
Animal |
Sex |
24HRS |
48HRS |
24HRS |
48HRS |
24HRS |
48HRS |
|
81 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
82 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
83 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
84 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
85 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
86 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
87 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
88 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
89 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
90 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
91 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
92 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
93 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
94 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
95 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
96 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
97 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
98 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
99 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
100 |
F |
0 |
0 |
0 |
0 |
0 |
0 |
|
0- No reaction
1- Scattered mild redness
2- Moderate and diffuse redness
3- Intense redness and swelling
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test substance is considered to be a mild skin sensitiser under the conditions of the test, but not sufficient for classification under CLP.
- Executive summary:
The sensitisation potential of the test substance was assessed in a study performed under GLP following the OECD 406 TG, using a method based on the maximisation test described by Magnusson and Kligman (1970). The study involved the treatment of guinea pigs using two procedures: the potential induction of an immune response and a challenge of that response. The sensitisation response of the animals was determined 1 and 2 days after challenge by assessing the degree of erythema.
Challenge of previously-induced guinea pigs with a 50% or a 25% w/v preparation of the test substance in com oil elicited a mild skin sensitisation response. Challenge of previously-induced guinea pigs with corn oil alone did not elicit a skin sensitisation response. A positive control study using hexylcinnamaldehyde demonstrated the sensitivity of the test system.
Based on these findings, the test substance is considered to be a mild skin sensitiser under the conditions of the test, but not sufficient for classification under CLP.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
