Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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.

Diss Factsheets

Administrative data

Description of key information

The main component of the substance “Reaction product of lead chloride or lead sulphate with alkaline solution” is lead (Pb). Pb salts used as source material are waste materials produced by Pb battery recycling process or by-products of the hydrometallurgical upgrading of PGM rich lead bullion. This transported isolated intermediate is produced under strictly controlled conditions, therefore there is no basis for further hazard assessment. It is an inorganic solid UVCB-substance having ~85% of particles smaller than 400 µm. The major and the most hazardous constituent of this intermediate is lead (conc. >50 %) which is determined to be poorly water soluble (section 4.8, EU method A.6), given that dissolution is widely considered to be required prior to percutaneous absorption, this may be interpreted as a likely indication of low bioavailability via the dermal exposure route.

Studies presented for skin sensitisation were performed with three selected lead compounds on an exemplary basis: lead oxide, dibasic lead phosphite and dibasic lead phthalate (Bien, 2003a,b,c). Rationality for selecting these compounds is exposure within industry, compound with inorganic anion and low solubility and compound with an organic anion with relatively high solubility, respectively. Lead compounds did not exhibit sensitative properties.

The classification is based on the composition of “Reaction product of lead chloride or lead suphate with alkaline solution” (see section 4.23), and assessed by using C&L rules for mixtures. All constituents in this intermediate having classification entries in CLP Annex VI were considered.  As a worst-case assumption all relevant compounds are considered leachable i.e. bioavailable.  The 100% distribution means that e.g. when 50 % Pb is present that all of it (100%) is allocated to the form of 'Pb compounds' and not a certain amount as e.g. PbCO3, which could result in a different classification.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

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
Reason / purpose for cross-reference:
data waiving: supporting information
Reason / purpose for cross-reference:
data waiving: supporting information
Reason / purpose for cross-reference:
data waiving: supporting information
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
August-December 2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Hypothesis for read-across: Lead (Pb) is the main component of the target substance, and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For toxicity assessment the bioavailable part is relevant. From the target substance itself, Pb is poorly soluble. For read-across purpose, however, data from more soluble compounds was used. Therefore, it is considered that the used read-across data gives worst-case estimate on the adverse effects. Well-documented and corresponded to the requirements of the recommended Annex V Test Guidelines.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
There was one deviation from the study protocol which was concerned with the relative humidity (section 6.2 Husbandry). At some days of the study the relative humidity was higher than 70%.
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An appropriate guinea pig maximization test is available, which would not justify conducting an additional LLNA due to animal welfare.
Species:
guinea pig
Strain:
other: pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation:
- Weight at study initiation: males: 459-545 g; females: 416-530 g
- Housing: The guinea pigs were kept in collective housing up to a maximum of 5 animals per cage in a battery of cages, equipped with a paper disposal system.
- Diet (e.g. ad libitum): "2040 Teklad Global Guinea Pig Diet" (pelleted diet, batch no. K080) offered ad libitum.
- Water (e.g. ad libitum): Tap water as for human consumption was continuously available ad libitum via drinking nipples.
- Acclimation period: 19 days (range finding); 22 days (main test)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 degrees centigrade
- Humidity (%): 37-76%
- Air changes (per hr): 16 times/ hour and filtered adequately
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light with light on at 7:00AM


IN-LIFE DATES: From: To:
Route:
intradermal and epicutaneous
Vehicle:
other: For the intradermal injection, the test article was diluted with aqua ad iniectabilia and Freund's complete adjuvant to a final concentration of 5%. For the dermal application, the solid test article was used as 50% formulation in petrolatum.
Concentration / amount:
Intradermal injection- 5% of the test article
Dermal application 50% in petrolatum
Route:
epicutaneous, occlusive
Vehicle:
other: For the intradermal injection, the test article was diluted with aqua ad iniectabilia and Freund's complete adjuvant to a final concentration of 5%. For the dermal application, the solid test article was used as 50% formulation in petrolatum.
Concentration / amount:
Intradermal injection- 5% of the test article
Dermal application 50% in petrolatum
No. of animals per dose:
10 test and 5 control animals
Details on study design:
RANGE FINDING TESTS: The range finding test was performed to determine the concentration of the test article to be used in the main test. For the intradermal injection, the test article was diluted with aqua ad iniectabilia (Delta-Pharma, Pfullingen) and Freund's complete adjuvant (FCA; batch no. 62K8933; SIGMA, Steinheim) to a final concentration of 5.0%. Two animals were employed, skin reactions being recorded 48 and 72 hours after treatment. For the dermal application, the solid test article was used 50% in petrolatum. A closed patch exposure was effected by means of an occlusive bandage using cellulose swabs, Leukosilk and non-irritating tape Elastoplast, which enveloped the whole animal's trunk. Two animals were employed and skin reactions were recorded 48 and 72 hours post applicationem.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 injection sites
- Exposure period: Seven days after injection, the injection sites were covered occlusively for 48 hours.
- Test groups: 10
- Control group: 5
- Site: Clipped intracapsular region on either side of the spine.
- Frequency of applications: Three pairs of intradermal injections (0.1 ml)
- Duration: Seven days later, the previous injection sites were covered occlusively for 48 hours with a patch carrying the test article (50%) or, in control animals, the control article petrolatum.
- Concentrations: Test Group: 1) FCA 50% (v/v) diluted in aqua ad iniectabilia, 2) testt article 5% in peanut oil, 3) test article 5% in aqua ad iniectabilia/FCA. Control Group: FCA 50% (v/v) diluted in aqua ad iniectabilia, 2) peanut oil, 3) peanut oil 50% (v/v) diluted in FCA.


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Both control and test animals were subjected to a challenge exposure 14 days after the second stage of the induction.
- Exposure period: 24 hours
- Test groups: 10
- Control group: 5
- Site: 5 x 5 cm clipped skin area on each flank
- Concentrations: The test article was applied at the concentration of 50% to the left flank and the control article petrolatum to the right in a volume of 0.5 g using the patch technique described under 6.2.1. In each case, the duration of the exposure was 24 hours under an occlusive dressing.
- Evaluation (hr after challenge): 24 and 48 hours after challenge.


OTHER:
Challenge controls:
Both control and test animals were subjected to a challenge exposure 14 days after the second stage of the induction. The challenge test was performed on a 5 x 5 cm clipped skin area on each flank. The test article was applied at the concentration of 50% to the left flank and the control article petrolatum to the right in a volume of 0.5 g using the patch technique described under 6.2.1. In each case, the duration of the exposure was 24 hours under an occlusive dressing.
Positive control substance(s):
yes
Remarks:
Assessed at least every 6 months by use of 25% and 50% "4-aminobenzoic acid ethyl ester (benzocaine)" (OECD406) in vaseline. The last test with acceptable levels of responses to this substance was performed from April 8 to 2 May 2003.
Positive control results:
Sensitisation rate (50%) at 24 hours: 70% Sensitisation rate (50%) at 48 hours: 70%
Sensitisation rate (25%) at 24 hours: 30% Sensitisation rate (25%) at 48 hours: 20%

Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No findings were observed in control animals.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
25% in vaseline
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
25% in vaseline
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
50% in vaseline
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
50% in vaseline
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:
test chemical
Dose level:
50% in petrolatum
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation

There were no skin reactions after the dermal application in the induction phase. No allergic skin reactions were observed in test animals after the challenge exposure 24 and 48 hours after patch removal. No findings were observed in control animals.

The sesitisation rate, i.e. the number of animals showing an alergic response expressed as a percentage of the total number of animals, was determined 24 and 48 hours after patch removal and was 0% in test animals in each case. The corresponding reaction rate in control animals was 0%.

Justification for read-across: Lead (Pb) is the main component of the target substance, and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For toxicity assessment the bioavailable part is relevant. From the target substance itself, Pb is poorly water soluble. For read-across purpose, however, data from more soluble compounds was used. Therefore, it is considered that the used read-across data gives worst-case estimate on the adverse effects.

See IUCLID Section 13 for Analogue approach report.

Interpretation of results:
GHS criteria not met
Conclusions:
According to the EEC Directive 2001/59/EEC, 6 August 2001 and the Gefahrstoffverordnung (GefStoffV) of 15 november 1999 (BGB1. I, p. 2233), the test article "ALLSTAB LP 3139 dibasic lead phosphite" can be classified as a "non-sensitiser since no allergic responses were observed in test animals after the adjuvant test according to Magnusson & Kligman.
Executive summary:

The potential skin sensitising properties of the test article "ALLSTAB LP 3139" were assessed in the guinea pig maximisation sensitisation test carried out as an adjuvant test according to the Magnusson & Kligman maximisation test method, using 10 test and 5 control animals in the main test. Following the induction exposure to the test article (50% in petrolatum) or the vehicle petrolatum (control article), the animals of both groups were subjected two weeks later to a challenge exposure with the test article (50% in petrolatum) as well as the control article. Responses to the challenge procedure were evaluated 24 and 48 hours after the end of the exposure period.

Results: No allergic reactions occurred in test animals 24 and 48 hours after the end of the challenge procedure. The sensitisation rate was 0%. No findings were observed in control animals (reaction rate: 0%).

Evaluation: According to nthe EEC Directive 2001/59/EEC, 6 August 2001 and the Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1. I, p.2233), the test article "ALLSTAB LP 3139 dibasic lead phosphite" can be classified as a "non-sensitiser" since no allergic responses were observed in test animals under the experimental conditions described.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
August-December 2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Hypothesis for read-across: Lead (Pb) is the main component of the target substance, and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For toxicity assessment the bioavailable part is relevant. From the target substance itself, Pb is poorly soluble. For read-across purpose, however, data from more soluble compounds was used. Therefore, it is considered that the used read-across data gives worst-case estimate on the adverse effects. Well-documented and corresponded to the requirements of the recommended Annex V Test Guidelines.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
Two deviations: No. 1 section 6.1 Animal Specification - Four control animals were used, since one of the male control animals died during the acclimatisation period. No.2: section 6.2 Husbandry - On some days the relative humidity was higher than 70%.
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An appropriate guinea pig maximization test is available, which would not justify conducting an additional LLNA due to animal welfare.
Species:
guinea pig
Strain:
other: pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation:
- Weight at study initiation: males 461-492 g; females: 405-484 g
- Housing: The guinea pigs were kept in collective housing up to a maximum of 5 animals per cage in a battery of cages, equipped with a paper disposal system.
- Diet (e.g. ad libitum): 2040 Teklad Global Guinea Pig Diet offerred ad libitum.
- Water (e.g. ad libitum):Tap water as for human consumption was continuously available ad libitum via drinking nipples.
- Acclimation period: 19 days (range finding); 22 days (main test)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 degrees centigrade. Maximum and minimum temperature and humidity were monitored daily.
- Humidity (%): The relative humidity was kept between 37 and 76%.
- Air changes (per hr): 16 times per hour and filtered adequately.
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light with light on at 7:00 AM.


IN-LIFE DATES: From: To:
Route:
intradermal and epicutaneous
Vehicle:
other: For the intradermal injection, the test article was diluted with aqua ad iniectabilia and Freund's complete adjuvant to a final concentration of 5%. For the dermal application, the solid test article was used as 50% formulation in petrolatum.
Concentration / amount:
Intradermal injection- 5% of the test article
Dermal application 50% in petrolatum
Route:
epicutaneous, occlusive
Vehicle:
other: For the intradermal injection, the test article was diluted with aqua ad iniectabilia and Freund's complete adjuvant to a final concentration of 5%. For the dermal application, the solid test article was used as 50% formulation in petrolatum.
Concentration / amount:
Intradermal injection- 5% of the test article
Dermal application 50% in petrolatum
No. of animals per dose:
10 test and 4 control animals
Details on study design:
RANGE FINDING TESTS: Two animals were employed and skin reactions were recorded 48 and 72 hours post applicationem. For the both the intradermal injection and the dermal application. For the intradermal injection, the test article was diluted with aqua ad iniectabilia and Freund's complete adjuvant to a final concemtration of 5%. Two animals were employed, skin reactions being recorded 48 and 72 hours after treatment. For the dermal application, the solid test article was used as 50% formulation in petrolatum. A closed patch exposure was effected by means of an occlusive bandage using cellulose swabs and non-irritating tape which enveloped the whole animal's trunk.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: Seven days after injections, the injection sites were covered occlusively for 48 hours.
- Test groups: 10
- Control group: 4
- Site: Injections were made in the clipped intracapsular region on either side of the spine
- Frequency of applications: Three pairs of intradermal injections (0.1 ml)
- Duration: Seven days later, the previous injection sites were covered occlusively for 48 hours with a patch carrying the test article (50%) or, in control animals, the control article petrolatum.
- Concentrations: Test Group 1) FCA 50% (v/v) diluted in aqua ad iniectabilia, 2) test article 5% in peanut oil, 3) test article 5% in aqua ad iniectabilia/F CA. Control group: 1) FCA 50% (v/v) diluted in aqua ad iniectabilia, 2) peanut oil, 3) peanut oil 50% (v/v) diluted in FCA.


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after the second stage of the induction
- Exposure period: 24 hours
- Test groups: 10 test animals
- Control group: 4 control animals
- Site: The challenge test was performed on a 5 x 5 cm clipped skin area on each flank.
- Concentrations: The challenge test was applied at the concentration of 50% to the left flank and the control article petroleum to the right in a volume of 0.5 g using the patch tehnique.
- Evaluation (hr after challenge): 24 and 48 hours after patch removal the appearance of the challenge and re-challenge skin sites was observed and skin responses were graffed on the basis of the classification system according DRAIZE. The animals were weighed before treatment and at the end of the study. All findings were recorded with respect to duration and severity on special report forms.


OTHER:
Challenge controls:
Both control and test animals were subjected to a challenge exposure 14 days after the second stage of the induction. The challenge test was performed on a 5 x 5 cm clipped skin area on each flank. The test article was applied at the concentration of 50% to the left flank and the control article petrolatum to the right in a volume of 0.5 g using the patch technique. In each case, the duration of the exposure was 24 hours under an occlusive dressing.
Positive control substance(s):
yes
Remarks:
Assessed at least every 6 months by use of 25% and 50% "4-aminobenzoic acid ethyl ester (benzocaine)" (OECD406) in vaseline. The last test with acceptable levels of responses to this substance was performed from April 8 to 2 May 2003.
Positive control results:
Sensitisation rate 50% at 24 h: 70% Sensitisation Rate 50% at 48 h: 70%
Sensitisation rate 25% at 24 h: 30% Sensitisation Rate 25% at 48 h: 20%
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No findings were observed in control animals.
Remarks on result:
no indication of skin sensitisation
Remarks:
Four control animals were used, since one of the male control animals died during the acclimatisation period.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
25% in vaseline
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
25% in vaseline
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
50% in vaseline
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
50% in vaseline
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:
test chemical
Dose level:
50% in petrolatum
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation

No allergic skin reactions occurred in test animals 24 and 48 hours after the end of the challenge procedure. The sensitisation rate was 0%. No findings were observed in control animals (reaction rate :0%).

Justification for read-across: Lead (Pb) is the main component of the target substance, and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For toxicity assessment the bioavailable part is relevant. From the target substance itself, Pb is poorly water soluble. For read-across purpose, however, data from more soluble compounds was used. Therefore, it is considered that the used read-across data gives worst-case estimate on the adverse effects.

See IUCLID Section 13 for Analogue approach report.

Interpretation of results:
GHS criteria not met
Conclusions:
According to the EEC Directive 2001/59/EEC, 6 August 2001 and the Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1. I, p. 2233) testconditions described, the test article "LITHARGE lead oxide" can be classified as a "non-sensitiser" since no allergic responses were observed in test animals under the experimental conditions described.
Executive summary:

The potential skin sensitising properties of the test article "LITHARGE lead oxide" were assessed in the guinea pig maximisation sensitisation test carried out as an adjuvant test according to the Magnusson & Kligman Maximisation test method, using 10 test and 5 control animals in the main test. Following the induction exposure to the test article (50% in petrolatum) or the vehicle petrolatum (control article), the animals of both groups were subjected two weeks later to a challenge exposure with the test article (50% in petrolatum) as well as the control article. Responses to the challenge procedure were evaluated 24 and 48 hours after the end of the exposure period.

Results: -No allergic skin reactions occurred in test animals 24 and 48 hours after the end of the challenge procedure. The sensitisation rate was 0%

-No findings were observed in control animals (reaction rate:0%).

Evaluation: According to the EEC Directive 2001/59/EEC, 6 August 2001 and the Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1. I, p.2233) test conditions described, the test article "LITHARGE lead oxide" can be classified as a "non-sensitiser" since no allergic responses were observed in test animals under the experimental conditions described.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
August-December 2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Hypothesis for read-across: Lead (Pb) is the main component of the target substance, and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For toxicity assessment the bioavailable part is relevant. From the target substance itself, Pb is poorly soluble. For read-across purpose, however, data from more soluble compounds was used. Therefore, it is considered that the used read-across data gives worst-case estimate on the adverse effects. Well-documented and corresponded to the requirements of the recommended Annex V Test Guidelines.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
There was one deviation from the study protocol which was concerned with the relative humidity section 6.2 Husbandry). On some days of the study the relative humidity was higher than 70%.
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An appropriate guinea pig maximization test is available, which would not justify conducting an additional LLNA due to animal welfare.
Species:
guinea pig
Strain:
other: pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles Rive Deutschland GmbH
- Age at study initiation:
- Weight at study initiation: males: 436-504 g; females: 395-481 g
- Housing: The guinea pigs were kept in collective housing up to a maximum of 5 animals per cage in a battery of cages, equipped with a paper disposal system.
- Diet (e.g. ad libitum): The animals received 2040 Teklad Global Guinea Pig Diet offered ad libitum.
- Water (e.g. ad libitum):Tap water as for human consumption was continuously available ad libitum via drinking nipples.
- Acclimation period: 19 days (range finding); 22 days ( main test)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-3 degrees centigrade
- Humidity (%): 37-76%
- Air changes (per hr): 16 times per hour and filtered adequately
- Photoperiod (hrs dark / hrs light): 12 hours dark/ 12 hours light with light on at 7:00 AM


IN-LIFE DATES: From: To:
Route:
intradermal and epicutaneous
Vehicle:
other: Intradermal application: The solid test article was diluted with aqua ad iniectabilia and Freund's complete adjuvant to a final concentration of 5%. Dermal Application-the solid test article was used 50% in petrolatum
Concentration / amount:
For the intradermal injection, the test article was diluted with aqua ad iniectabilia and Freund's complete adjuvant to a final concentration of 5%. For the dermal application, the solid test article was used 50% in petrolatum.
Route:
epicutaneous, occlusive
Vehicle:
other: Intradermal application: The solid test article was diluted with aqua ad iniectabilia and Freund's complete adjuvant to a final concentration of 5%. Dermal Application-the solid test article was used 50% in petrolatum
Concentration / amount:
For the intradermal injection, the test article was diluted with aqua ad iniectabilia and Freund's complete adjuvant to a final concentration of 5%. For the dermal application, the solid test article was used 50% in petrolatum.
No. of animals per dose:
10 test and 5 control animals
Details on study design:
RANGE FINDING TESTS: The range finding test was performed to determine the concentrations of the test article to be used in the main test. For the intradermal injection, the test article was diluted with aqua ad iniectabilia and Freund's complete adjuvant to a final concentration of 5%. Two animals were employed, skin reactions being recorded 48 and 72 hours after treatment. For the dermal application, the solid test article was used 50% in petrolatum. A closed patch exposure was effected by means of an occlusive bandage using swabs, Leukosilk, and non-irritating tape Elastoplast which enveloped the whole animal's trunk. Two animals were employed and skin reactions were recorded 48 and 72 hours post applicationem.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: Seven days after the injection, the injection sites were covered occlusively for 48 hours.
- Test groups: 10 guinea pigs
- Control group: 5 guinea pigs
- Site: Injections were made in the clipped intracapsular region on either side of the spine.
- Frequency of applications: Three pairs of intradermal injections (0.1 ml)
- Duration: Seven days after the injection, the injection sites were covered occlusively for 48 hours with a patch carrying the test article (50%) or, in control animals, the control article petrolatum.
- Concentrations: Test group: 1) FCA 50% (v/v) diluted in aqua ad iniectabilia, 2) test article 5% in peanut oil, 3) test article 5% in aqua iniectabilia/FCA. Control group: 1) FCA 50% (v/v) diluted in aqua ad iniectabilia, 2) peanut oil, 3) peanut oil 50% (v/v) diluted in FCA.




B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after the second stage of the induction
- Exposure period: 24 hours
- Test groups: 10 test animals
- Control group: 5 control animals
- Site: The challenge test was performed on a 5 x 5 cm clipped skin area on each flank.
- Concentrations: The test article was applied at the concentration of 50% to the left flank and the control article petrolatum to the right in a volume
of 0.5 g using the patch technique. In each case, the duration of exposure was 24 hours under an occlusive dressing.
- Evaluation (hr after challenge): 24 and 48 hours after patch removal the appearance of the challenge and re-challenge skin sites was observed and skin responses were gradfed on the basis of the classification system according DRAIZE. The animals werer weighed before treatment and at the end of the study. Al findings were recorded with respect to duration and severity on special report forms.




OTHER:
Challenge controls:
The control article petrolatum was applied to the left flank of the guinea pig in a volume of 0.5 g using the patch technique for 24 hours under an occlusive dressing.
Positive control substance(s):
yes
Remarks:
Assessed at least every 6 months by use of 25% and 50% "4-aminobenzoic acid ethyl ester (benzocaine)" (OECD406) in vaseline. The last test with acceptable levels of responses to this substance was performed from April 8 to 2 May 2003.
Positive control results:
Sensitisation rate (50%) at 24 h: 70% Sensitisation rate (50%) at 48h: 70%
Sensitisation rate (25%) at 24 h: 30% Sensitisation rate (25%) at 24h: 30%
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No findings were observed in control animals.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50% in petrolatum
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% in petrolatum. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
25% in vaseline
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
25% in vaseline
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
50% in vaseline
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
50% in vaseline
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

There were no skin reactions after the dermal application in the induction phase. No allergic skin reactions were observed in the test animals after the challenge exposure 24 and 48 h after patch removal. No findings were observed in control animals. The sensitisation rate, i.e. the number of animals showing an allergic response expressed as a percentage of the total number of animals, was determined 24 and 48 h after patch removal and was 0% in test animals in each case. The corresponding reaction rate in control animals was 0%.

Justification for read-across: Lead (Pb) is the main component of the target substance, and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For toxicity assessment the bioavailable part is relevant. From the target substance itself, Pb is poorly water soluble. For read-across purpose, however, data from more soluble compounds was used. Therefore, it is considered that the used read-across data gives worst-case estimate on the adverse effects.

See IUCLID Section 13 for Analogue approach report.

Interpretation of results:
GHS criteria not met
Conclusions:
According to the EEC Directive 2001/59/EEC, 6 August 2001 and the Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1. I, p. 2233), thetest article PEBETAL dibasic lead phthalate can be classified as a "non-sensitiser" since no allergic responses were observed in test animals after the adjuvant test according to Magnusson & Kligman.
Executive summary:

The potential skin sensitising properties of the test article PEBETAL dibasic lead phthalate were assessed in the guinea pig maximisation test method, using 10 test and 5 control animals in the main test. Following the induction exposure to the test article (50% in petrolatum) or the vehicle petrolatum (control article), the animals of both groups were subjected two weeks later to a challenge with the test article (50% in petrolatum) as well as the control article. Responses to the challenge procedure were evaluated 24 and 48 h after the end of the exposure period.

Results: - No allergic skin reactions occurred in test animals 24 and 48 h after the end of the challenge procedure. The sensitisation was 0%.

-No findings were observed in control animals (reaction rate: 0%).

According to the EEC Directive 2001/59/EEC, 6 August 2001 and the Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1 I. p. 2233), the test article PEBETAL dibasic lead phthalate can be classified as a "non-sensitiser" since no allergic responses were observed in test animals under the experimental conditions described.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Justification for read-across: Lead (Pb) is the main component of the target substance, and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For toxicity assessment the bioavailable part is relevant. From the target substance itself, Pb is poorly water soluble. For read-across purpose, however, data from more soluble compounds was used. Therefore, it is considered that the used read-across data gives worst-case estimate on the adverse effects.
See IUCLID Section 13 for Analogue approach report.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reading:
other: Read-across conclusion
Remarks on result:
no indication of skin sensitisation
Remarks:
This conclusion is based on the results of the in vivo studies performed the 3 test articles (Lead monoxide, [phthalato(2-)]dioxotrilead and trilead dioxide phosphonate). The tests with the three latter substances were performed according to non-LLNA methods.
Interpretation of results:
GHS criteria not met
Conclusions:
When administered to the eye, the 3 test articles (Lead monoxide, [phthalato(2-)]dioxotrilead and trilead dioxide phosphonate) are classified as "non sensitizing to the skin".
Based on the similarities between these three test articles and the target substance described in the read-across jsutification inculded in section 13, the target substance is considered to be "non sensitizing to the skin".
Endpoint conclusion
Additional information:

Justification for read-across: Lead (Pb) is the main component of the target substance, and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For toxicity assessment the bioavailable part is relevant. From the target substance itself, Pb is poorly water soluble. For read-across purpose, however, data from more soluble compounds was used. Therefore, it is considered that the used read-across data gives worst-case estimate on the adverse effects. See IUCLID Section 13 for Analogue approach report.

Studies (Bien a,b,c 2003) exhibit no sensitisation potential on skin. The lack of toxicity, irritation or reports of sensitisation from occupational exposure settings, do not appear to pose risk of sensitisation and classification for these endpoints is not indicated. Lead and sparingly soluble lead compounds do not raise a concern since

dissolution is widely considered to be required prior to percutaneous absorption, this may be interpreted as a likely indication of low bioavailability via the dermal exposure route.

The classification is based on the composition of “Reaction product of lead chloride or lead suphate with alkaline solution” (see section 4.23), and assessed by using C&L rules for mixtures. All constituents in this intermediate having classification entries in CLP Annex VI were considered. As a worst-case assumption all relevant compounds are considered leachable i.e. bioavailable. The 100% distribution means that e.g. when 50 % Pb is present that all of it (100%) is allocated to the form of 'Pb compounds' and not a certain amount as e.g. PbCO3, which could result in a different classification.

Calculated classification was performed from all constituents in this intermediate having classification entries in CLP Annex VI (using mixture toxicity rules) with MeClas-tool. For sensitisation no major drivers were designated, thus no classification.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The derived classification result for the UVCB substance with calculation with C&L mixture rules by Meclas-tool is:

CLP: Not classified for sensitisation properties.

See section 13 "Assessment Reports" for details of MeClas-classification approach.