Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion:
Based on the determination of the pH of 6.54, the determination of the acidic/alkaline reserve of lanthanum acetate was not applicable. Based on the pH-value the substance was considered not to be corrosive (Groicher, 2012). On the basis of both an in vitro skin corrosion and an in vitro skin irritation test, the substance is considered respectively non-corrosive and non-irritant to skin (Warren 2013 and Warren 2013). In addition, no skin irritation is observed after dermal exposure to a single dose of 2000 mg/kg bw (Bradshaw, 2013). Therefore, and based on the data available ('Weight-of-Evidence' approach), no in vivo test is warranted and it is decided not to classify the substance for skin irritation.
Eye irritation:
For eye irritation, an in vitro BCOP test was performed, indicating that the substance is corrosive to eyes (Warren, 2013c). No further in vivo testing is warranted.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 November 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented GLP study following OECD Guideline 437 with no deviations.
Qualifier:
according to
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
other: isolated bovine cornea
Strain:
other: not applicable
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Eyes from freshly slaughtered adult cattle as a by-product of normal operation
- Age at study initiation: 12-60 months
Vehicle:
physiological saline
Controls:
yes, concurrent vehicle
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 µL
- Concentration (if solution): 20% w/v of test item in 0.9% w/v sodium chloride solution

VEHICLE
- Amount(s) applied (volume or weight with unit): 750 µL
- Concentration (if solution): 0.9% w/v sodium chloride solution
Duration of treatment / exposure:
240 minutes
Observation period (in vivo):
At the end of the incubation period each cornea was examined for defects. Only corneas free of damage were used.
At the end of the exposure period the test item preparation and control items were removed from the anterior chamber and the cornea was rinsed three times with fresh complete MEM containing phenol red before a final rinse with complete MEM. The anterior and posterior chambers were refilled with fresh complete MEM. A post-treatment opacity reading was taken and each cornea was visually observed. The corneas were visually observed for macroscopic damage (eg pitting/sloughing) caused by the test item or controls.
Number of animals or in vitro replicates:
3 corneas per test item, positive control, and vehicle
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Rinsed 3 times with fresh minimum essential medium (MEM) containing phenol red before a final rinse with complete MEM
- Time after start of exposure: 240 minutes

Scoring system: results from the two endpoints were combined to generate an In Vitro Irritancy score.
In Vitro Irritancy Score = mean opacity value + (15 x mean OD492 value)
A test item that induces an In Vitro Irritancy score >= 55.1 is considered on ocular corrosive or severe irritant.

TOOL USED TO ASSESS SCORE: Opacitometer/ fluorescein
Irritation parameter:
in vitro irritation score
Value:
60.7
Negative controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
The positive control In Vitro Irritancy Score was within the range of 55.8 to 126.1. The positive acceptance criterion was therefore satisfied.
The corneas treated with the negative control item was clear post incubation (In Vitro Irritancy Score: 3.1).
Irritant / corrosive response data:
In Vitro Irritancy score - test item: 60.7
In Vitro Irritancy score-negative control: 3.1, clear
In Vitro Irritancy score-positive control: 81.6. (Historical range 55.8-126.1, acceptable), cloudy

In Vitro Irritancy score - test item: 60.7

In Vitro Irritancy score-negative control: 3.1, clear

In Vitro Irritancy score-positive control: 81.6. (Historical range 55.8-126.1, acceptable), cloudy

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item was found to be an ocular corrosive or severe irritant (In Vitro Irritancy score >/= 55.1).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

First, the pH-value was measured electrochemically with a calibrated pH meter at 20 ± 1°C (Groicher T, 2012). The obtained pH-value was the basis for deciding if it was necessary to determine the acid reserve. Prior to measurement, the pH meter was calibrated via a three-point calibration with a buffer in the expected measurement range. The pH was determined three times from a 10% solution of the lanthanum acetate under continuous stirring.

The pH was protocolled. As the pH-value was determined to be 6.54, the determination of the acid reserve was not applicable.

An in vitro skin corrosion test (Warren, 2013) and in vitro skin irritation test (Warren, 2013) were performed according to OECD guidelines 431 and 439 respectively with lanthanum acetate. On the basis of the relative mean viability of the treated tissues, the test item was considered to be non-corrosive and non-irritating to the skin.

In an acute dermal toxicity study, lanthanum acetate was tested up to 2000 mg/kg bw (Bradshaw, 2013) showing no signs of dermal irritation. According to the REACH Regulation (column 2, annex VIII, section 8), an in vivo skin irritation study does not need to be conducted if, in an acute toxicity study by the dermal route, no skin irritation is indicated up to the limit dose level (2000 mg/kg bw). Therefore, it is not necessary to perform an in vivo skin irritation study.

Eye irritation

Warren (2013c) performed a Bovine Corneal Opacity and Permeability Assay (BCOP) (OECD 437). In this test, 3 bovine corneas were exposed to lanthanum acetate during 240 minutes. After exposure, corneas were rinsed and opacity and permeability were measured immediately. Both vehicle and positive control were considered to be valid. The in vitro irritancy score is 60.7 (> 55.1). Therefore, the substance was found to be an ocular corrosive or severe irritant. On the basis of this in vitro test result, the substance will be classified as eye damage Cat 1. Therefore, no further in vivo testing is warranted (REACH Regulation, Annex VIII, Section 8.2.1, Column 2).


Justification for selection of skin irritation / corrosion endpoint:
No study is selected as a weight of evidence is built.

Justification for selection of eye irritation endpoint:
There is only one study available

Effects on eye irritation: corrosive

Justification for classification or non-classification

Based on the in vitro test results and the absence of skin irritation in the acute dermal toxicity study and according to the criteria of the DSD and CLP Regulation, lanthanum acetate should not be classified as irritating to the skin.

Based on the in vitro test results on eye irritation / corrosion and according to the criteria of the DSD and CLP Regulation, lanthanum acetate should be classified for risk of serious damage to eyes R41 and as eye damage Cat 1.