Lead Carbonate Intermediate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

August 2002-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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Trilead dioxide phosphonate

EC Number:

235-252-2

EC Name:

Trilead dioxide phosphonate

Cas Number:

12141-20-7

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): ALLSTAB LP 3139 dibasic lead phosphite
- Molecular formula (if other than submission substance): 2PBO X PbPO3 X 0,5 H2O
- Physical state: fine white powder
- Analytical purity: 99.3%
- Composition of test material, percentage of components: 82.7% Pb; 0.2% water
- Lot/batch No.: 210510067
- Expiration date of the lot/batch: 24 months after shipping
- Storage condition of test material: At room temperature; minimum 24 months (after shipment), when stored insealed containers at temperatures below 40 degrees.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

The health status of the animals is SPF. Animals have been housed at the testing facility for 27 days or several months. Three male rabbits. Before the animals arrived, the study room and cages were cleaned and disinfected. During the study, the room and cages were cleaned at regular intervals. The rabbits were kept individually in a battery of cages with a cage size of 100 x 45 x 40 cm (L x B x H), equipped with a paper disposal system. The room temperature was adjusted to 20 C.+/_ 3 and the relative humidity was kept between 30 and 70%. Maximum and minimum temperature and humidity were monitored daily. Artificial light was set to give a cycle of 12 hours light and 12 hours dark with light on at 7:00 a.m. Air was changed about 16 times per hour. and filtered adequately. The animals received Teklad Global Rabbit Diet. Tap water as for human consumption was continuously available ad libitum via drinking nipples.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1g
- Concentration (if solution):


VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

Three male rabbits used in the test were acclimatised to laboratory conditions for 27 days or several months. Twenty four hours before treatment, the eyes of all animals were examined for potential ocular lesions. Since the animals did not show ocular abnormalities, they were allocated to the test. The solid test article was used as supplied by the Sponsor. One of the animals (rabbit no.1) was treated in advance in order to assess ocular reactions to the test article. The animal was treated with 0.1 g of the solid test article, which was introduced into the conjunctival sac of the right eye after gently pulling the lower lid away from the eyeball. The lid was then gently held together for about 1 sec in order to limit loss of the test article. The untreated left eye served as the control. Since there was no remarkable response to the instillation of the test article within a few days, the further two animals were treated subsequently in the same manner. Ocular reactions were assessed 1, 24, 48, and 72 hours after instillation according to the "Grades for ocular lesions." In addition to the examination of the eyes, general clinical observation was conducted.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 72h

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 72h

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 72h

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 72h

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Reversibility:

fully reversible within: 72h

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Reversibility:

fully reversible within: 72h

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

iris score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Irritant / corrosive response data:

Redness of the conjunctivae, grade 1 or 2, were observed in the animals at 1 hour after instillation. These findings were still apparent in two out of the three animals until 24 or 48 hours after instillation.
Additionally, slight discharge was observed in all animals at 1 hour after instillation and in one out of three animals also at 24 hours after instillation.
The mean grades were 0.0, 1.00 and 1.00 for redness of the conjunctivae and 0.0, 0.67and 0.33 for chemosis of the conjunctivae.

Other effects:

No general toxic effects were observed. The observed findings were fully reversible 72 hours after instillation in all animals.

Any other information on results incl. tables

The mean grades of ocular reactions at 24, 48, and 72 hours after instillation were lower than classified as irritant by the EEC Directive 2001/59/EEC of 6 August 2001 and the Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1. I, p. 2233).

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.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The mean grades of ocular reactions at 24, 48 and 72 hours after instillation were lower than the value classified as irritant by the EEC Directive 2001/59/EEC of 6 August 2001 and the Gefahstoffverordnung (GefStoffV) of 15 November 1999 (BGB1. I, p. 2233). When administered to the eye, the test article "ALSTAB LP 3139 dibasic lead phosphite" may be classified as "non-irritant."

Executive summary:

The potential toxicity of "ALSTAB LP 3139 dibasic lead phosphite" was assessed in an acute eye irritation/corrosion test on 3 albino rabbits. In each animal, 0.1g of the test article was introduced into the conjunctival sac of the right eye, the untreated left eye served as control. Both eyes were examined at 1, 24, 48 and 72 hours post applicationem. The following results were obtained:

Redness and chemosis of the conjunctivae, grade 1 nad 2, were observed in the animals at 1 hour after instillation. These findings were still apparent in two out of the three animals until 24 or 48 hours after instillation. Additionally, slight discharge was observed in all animals at 1 hour after instillation and in one out of three animals also at 24 hours after instillation. No general toxic effects were observed. The observed ocular findings were fully reversible 72 hours after instillation in all animals. The mean grades were 0.0, 1.00, and 1.00 for redness of the conjunctivae and 0.0, 0.67 and 0.33 for chemosis of the conjunctivae.

The mean grades of ocular reactions at 24, 48, 72 hours after instillation were lower than the value classified as irritant by the EEC Directive 2001/59/EEC of 6 August 2001 and the Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGN1. I, p.2233). When administered to the eye, the test article "ALSTAB LP 3139 dibasic lead phosphite may be classified as "non-irritant."