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Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 November 2005 to 7 December 2005
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA
Sex:
female
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
Sighting study: 1, 5, 10, 25 and 50% (w/v) LLNA: 1, 2.5, 5% (w/v)
No. of animals per dose:
5 female mice/dose
Parameter:
SI
Value:
3.4
Test group / Remarks:
Test Group III
Parameter:
SI
Value:
1.4
Test group / Remarks:
Test Group I
Parameter:
SI
Value:
1.5
Test group / Remarks:
Test Group II

LLNA

All animals appeared normal for the duration of the study. Individual DPM counts are presented below.

 

The application of the test material at a concentration of 2% (w/v) resulted in an increase in isotope incorporation which was 3.0 times that of the vehicle control. Consequently the test substance was shown to be a potential skin sensitiser.

 

The positive control produced an acceptable response.

 

Table 7.4.1 -1: Average disintegrations per minute per mouse

Conc. of test material

(% w/v)

Average disintegrations/minute (dpm) per mouse

Test : control ratio (SI)

0

565

-

1

781

1.4

2.5

870

1.5

5

1899

3.4

Positive control

7222

12.8

 

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
In conclusion Profenofos Technical (Batch P03) produced a stimulation index >3 in one group of test animals, and is therefore consdiered a skin sensitiser under the conditions of this study.
Executive summary:

A skin sensitisation study was conducted on 3 groups of 5 female mice to determine if Profenofos Technical (Batch P03) possessed a significant potential to cause skin sensitisation. Test groups were treated with an appropriate dilution (0.5, 1 or 2% w/v) in a 80% acetone:20% olive oil vehicle. Each animal recieved 25 uL to the dorsum of each ear. The animals were treated once daily for three days. Two days post the final application, animals were injected with tritiated methyl-thymidine via the tail vein. Five hours later the animals were sacrificed and the draining auricular lymph nodes removed and prepared for cell suspension and scintillation counting. A vehicle control group of 5 animals was run concurrently. A positive control group of 5 animals was also run concurrently, treated with 90% alpha-hexylcinnamaldehyde in vehicle.

 

In conclusion Profenofos Technical (Batch P03) produced a stimulation index >3 in one group of test animals, and is therefore consdiered a skin sensitiser under the conditions of this study.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
11 November 1996 to 5 December 1996
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
male/female
Route:
intradermal and epicutaneous
Vehicle:
peanut oil
Concentration / amount:
Pretest: 0.5, 1, 3, 5% (w/v) GPMT: Intradermal injection: 3% (w/v) Induction: 30% (w/v) Challenge: 5% (w/v)
Route:
epicutaneous, occlusive
Vehicle:
peanut oil
Concentration / amount:
Pretest: 0.5, 1, 3, 5% (w/v) GPMT: Intradermal injection: 3% (w/v) Induction: 30% (w/v) Challenge: 5% (w/v)
No. of animals per dose:
Control gp: 5 animals/sex/gpTest gp: 10 animals/sex/gp
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Vehicle
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
3%
No. with + reactions:
6
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 3%. No with. + reactions: 6.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
3%
No. with + reactions:
9
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 3%. No with. + reactions: 9.0. Total no. in groups: 20.0.
Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Based on the results of this study, CGA15324 tech. is concluded to be a skin sensitiser.
Executive summary:

In a dermal sensitisation study, guinea pigs (10/sex) received intradermal injections of 3% (w/v)CGA15324 tech.in peanut oil along with injections of Freund’s Complete Adjuvant (FCA) and 3% (w/v)CGA15324 tech.in FCA. The treatment regime involved induction of sensitization by intradermal injection on day 1, induction of sensitisation by topical administration on day 8 (30% (w/v)CGA15324 tech., challenge by topical administration on day 22 (5%CGA15324 techin vaseline).

 

Following challenge, dermal scores of 1 were noted in 6/20 and 9/20 test animals at the 24 hour and 48 hour scoring intervals, respectively, which corresponded to a sensitisation rate of 45%, which is above the 30% threshold limit. Dinitrochlorobenzene (DCNB) demonstrated a positive response. 

 

Based on the results of this study, CGA15324 tech. is concluded to be a skin sensitiser.

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
9 August 2005 to 16 August 2005
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA
Sex:
female
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
Sighting study: 1, 5, 10, 25 and 50% (w/v) LLNA: 1, 2.5, 5% (w/v)
No. of animals per dose:
4 female mice/dose
Parameter:
SI
Remarks on result:
other: refer to results section
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: refer to results section

Sighting study

Only the 1 and 5% (w/v) dose groups showed signs of systemic toxicity

 

LLNA

Study groups exposed to 2.5 and 5% (w/v) were terminated due to signs of systemic toxicity approaching the study severity limit. Animals in these groups showed a lethargy and had a hunched/pinched appearance and lack of lustre in the eyes indicative of a general loss of wellbeing.

 

The application of the test material at a concentration of 1% (w/v) resulted in an increase in isotope incorporation which was 3.0 times that of the vehicle control. Consequently the test substance was shown to be a potential skin sensitiser.

 

The positive control produced an acceptable response.

 

Table 7.4.1 -2: Averge distintegrations per minute per mouse 

Conc. of test material

(% w/v)

Number of lymph nodes assayed

Disintegrations/minute (dpm)

dpm/lymph node

Test : control ratio (SI)

0

8

3294

412

n/a

1

8

9963

1245

3.0

2.5

-

-

-

-

5

-

-

-

-

2.5 and 5% (w/v) dose groups terminated prior to end of study due to toxicity

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
In conclusion Profenofos Technical Goa Origin is a skin sensitiser under the conditions of this study.
Executive summary:

A sample of Profenofos Technical Goa Origin was assessed for its skin sensitisation potential using the mouse LLNA. The assay determines the level of T lymphocyte proliferation in the lymph nodes draining the site of chemical application, by measuring the amount of radiolabelled thymidine incorporated into the dividing cells. The test substance was applied as 1, 2.5 or 5% (w/v) preparations in acetone in olive oil (4:1). A vehicle control group was similarly treated using acetone in olive oil (4:1) alone. Dose levels were set in accordance with toxicity and sighting study data.

The test substance had the capacity to cause skin sensitisation when applied as a 1% (w/v) preparation in acetone in olive oil (4;1). Test groups for the 2.5 and 5% (w/v) dose levels were terminated prior to the end of study due to the onset of toxicity.

In a postive contol study, hexylcinnamaldehyde was shown to have the capacity to cause skin sensitisation when applied as 10% or 25% (w/v) preparations in acetone in olive oil (4:1), confirming the validity of the protocol used for this study.

In conclusion Profenofos Technical Goa Origin is a skin sensitiser under the conditions of this study.

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

Of the two local lymph node assays conducted on different purities of Profenofos (Kuhn, 2005 - purity 97.3%; Betts, 2005 - purity 92.1%) and the guinea pig maximisation test conducted (Winkler, 1996 - purity 91.2%) all confirm that Profenofos is a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

It is recognised that both acute and repeat inhalation exposure studies to Profenofos provide compelling evidence that the test material causes irritation of the respiratory tract. However from the available studies there is no evidence of potential respiratory sensitisation (which is manifest as laboured breathing, rhinitis, alveolitis etc). Furthermore available human data do not suggest that the test material would be a respiratory sensitiser.

 

Workers engaged in the manufacture of Profenofos were given a medical examination annually between 1980 and 1998. No health effects related to exposure of Profenofos were identified.

 

The EPA reviewed the Incident Data System (IDS) to determine whether Profenofos cases had been reported. The database contains over 17,000 pesticide-related reports of incidents involving adverse effects to humans and approximately 9,000 reports involving domestic animals since 1992. Of the reported incidents, Profenofos was identified in only seven human cases with minor symptoms and one lawsuit alleging death (EPA, 2000).

 

Whilst no studies are available which assess pulmonary function in animals or humans following repeated exposure, available evidence confirms that Profenofos causes respiratory irritation, no evidence of sensitisation of the respiratory tract has been reported. The chemical structure does not contain a diisocynate group or other structural alerts (i.e. acid anhydride, platinum salt).

 

References:

US EPA (2000). Interim Reregistration Eligibility Decision (IRED) for Profenofos case no. 2540.

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008 Profenofos is a skin sensitiser.