Calcium acetylide

Endpoint summary

Description of key information

Skin irritation: Two OECD 404 studies on calcium hydroxide (Bien, 1994; Vaeth, 2004);

determination of the alkali reserve og 10 % CaC2 solution (Möller, 2011).
Eye irritation: Two OECD 405 studies on calcium hydroxide (de Jouffrey, 1995); case report on accidential exposure to CaC2 (Testud, 2002).

Respiratory irritation: Several epidemiological studies on calcium hydroxide/oxide/lime (SCOEL, 2008); studies in human volunteers exposed to CaO (Cain, 2004, 2008).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

As calcium carbide instantly hydrolyses to Ca(OH)2 and C2H2 upon contact with water/moisture the assessment is based on the degradation products. For details please refer to the read across report in section 13.

Reason / purpose for cross-reference:

read-across source

Vehicle:

unchanged (no vehicle)

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: Average scores recorded after 24, 48 and 72 hours after a 4-hour application.

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

other: Average scores recorded after 24, 48 and 72 hours after a 4-hour application.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

other: Average scores recorded after 24, 48 and 72 hours after a 4-hour application.

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

other: Average scores recorded after 24, 48 and 72 hours after a 4-hour application.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: Average scores recorded after 24, 48 and 72 hours after a 4-hour application.

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Remarks on result:

other: Average scores recorded after 24, 48 and 72 hours after a 4-hour application.

Irritant / corrosive response data:

After a maximum 4-hour exposure of calcium hydroxide (hydrated lime) in putty form (60 % H2O, 40 % Ca(OH)2) to the skin of
the three test animals (Nos. 2692, 2632 and 2616) no skin corrosion but the following symptoms of irritation were observed
during the subsequent 14-day observation period.
The animal No. 2692 used in the initial test showed a very slight erythema on the middle (1 h exposure period) and posterior
(4 h exposure period) left test field immediately after the application.
1 h after termination of exposure a well defined erythema was observed on the posterior (4 h exposure period) left test field of
the animal No. 2692 used in the initial test. Animal No. 2616 showed very slight erythema on the anterior left test field,
whereas no skin reaction was observed at the remaining animal No. 2632.
24 and 48 h after termination of exposure the animal No. 2692 used in the initial test showed a well defined erythema on the
middle (1 h exposure period) and posterior (4 h exposure period) left test field. A well defined erythema and a very slight
oedema were oberved on the anterior left test field of another animal No. 2632. The remaining animal No. 2616 showed no
signs of skin irritation.
72 h after termination of exposure a very slight erythema was observed on the middle (1 h. exposure period) left test field of
the animal No. 2692 used in the initial test and a well defined erythema on the posterior left test field. Another animal No. 2632
showed a well defined erythema and a very slight oedema on the anterior left test field, whereas no skin reactions were
observed at the remaining animal No. 2616.
7 days after termination of exposure animal No. 2632 showed a well defined erythema on the anterior left test field. The animal
No. 2692 used in the initial test was free of any skin reactions, whereas on day 6 a very slight erythema was still observed on
the middle (1 h exposure period) and posterior (4 h exposure period) left test field. The remaining animal No. 2616 did not
show any signs of skin irritation, too.
14 days after the termination of exposure animal No. 2632 was also free of any skin reactions.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Based on the results of the study described in this report and according to the EC Regulation No. 1272/2008 and subsequent
regulations, calcium hydroxide (hydrated lime) in putty form (60 % H2O, 40 % Ca(OH)2), shall be classified as irritating.

Executive summary:

In a primary dermal irritation study performed according to OECD TG 404, 3 Himalayan rabbits were dermally exposed to 0.5g of calcium hydroxide (unchanged) for 3 minutes, 1 hour and 4 hours to an area of 2.5cm x 2.5cm. Animals were then observed for 14 days. Irritation was scored by the method of Draize.

After a maximum 4-hour exposure to the test item, no skin corrosion was observed. However, there were signs of irritation indicated by erythema and slight edema formation, which subsided after 7 and 14 days of observation.

Signs of skin irritation were fully reversible until the end of the observation period.

In this study, calcium hydroxide (hydrated lime) is a dermal irritant. According to the criteria set out in Regulation (EC) No. 1272/2008, classification of calcium hydroxide as Skin Irrit. 2 is warranted.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reference 2

Endpoint:

skin irritation / corrosion, other

Remarks:

other: acid/alkali reserve

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

according to guideline

Guideline:

other: Young et al.

Principles of method if other than guideline:

J.R. Young et al Classification as corrosive or irritant to skin of preparations containing acid or alkaline substances, without testing on animals. Toxic. in Vitro Vol. 2, No. 1, pp. 19-26, 1988.

GLP compliance:

yes

Species:

other: not applicable, determination of acid/alkali reserve

Strain:

other: not applicable, determination of acid/alkali reserve

Details on test animals or test system and environmental conditions:

not applicable, determination of acid/alkali reserve

Type of coverage:

other: not applicable, determination of acid/alkali reserve

Preparation of test site:

other: not applicable, determination of acid/alkali reserve

Vehicle:

other: not applicable, determination of acid/alkali reserve

Controls:

other: not applicable, determination of acid/alkali reserve

Amount / concentration applied:

not applicable, determination of acid/alkali reserve

Duration of treatment / exposure:

not applicable, determination of acid/alkali reserve

Observation period:

not applicable, determination of acid/alkali reserve

Number of animals:

not applicable, determination of acid/alkali reserve

Details on study design:

See below

Irritation / corrosion parameter:

other: alcaline reserve

Run / experiment:

#1

Value:

ca. 12.48

Vehicle controls validity:

not valid

Negative controls validity:

not valid

Positive controls validity:

not valid

Remarks on result:

other: For test of alcaline reserve the given test criteria aren't valide

1) Acid/alkali reserve

Table 1 shows the determined values of the alkali reserve of the 10% test item solution.

Table 1: Alkali reserve of test item

Test	pH (start)	alkali reserve	"classification value" for corrosive	"classification value" for irritant
1	12.3	13.8	13.5	14.6
2	11.9	14.1	13.1	14.2
3	12.3	14.0	13.5	14.6
4	12.7	14.2	13.9	15.1
5	12.6	14.1	13.8	15.0
Mean value		14.1	13.5	14.7
Standard deviation		0.1	0.3	0.3

The mean values are calculated from the original data and not from the rounded values, which are shown in Table 1.

Based on the values shown in Table 1 with 13.5 < 14.5 (limit for corrosive] the test item is not corrosive. With 14.7 > 3 (limit for irritant) the classification of the test item can be estimated to be irritant.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The test item has an alkali reserve of 14.1. According to the method described by Young et al. the classification of the test item can be estimated to be irritant.

Executive summary:

The method of acid/alkaline reserve described by Young et al. can assist the classification of a test item without the use of test methods involving animals. It is based on the measurement of the pH of an aqueous solution of the test item and the titration up or down to a specific pH value.

Definition of the acid/alkali reserve: for acidic preparations, this is the amount [g] of sodium hydroxide/100 g of preparation required to produce a specified pH-value. For alkaline preparations, it is the amount [g] of sodium hydroxide equivalent to the g sulphuric acid/100 g of preparation required to produce a specified pH-value.

Classification of the test item:The classification can be estimated by means of the pH value of the test item solution and the acid/alkali reserve:

- If pH+1/12 alkali reserve >/= 14.5 or pH-1/12 acid reserve </= -0.5, the preparation can be classified as corrosive

- For preparations not classified as corrosive on this basis, if pH+1/6 alkali reserve >/= 13 or pH-1/6 acid reserve </= 1, the preparation can be classified as irritant.

The test item has an alkali reserve of 14.1. According to the method described by Young et al. the classification of the test item can be estimated to be irritant.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

As calcium carbide instantly hydrolyses to Ca(OH)2 and C2H2 upon contact with water/moisture the assessment is based on the degradation products. For details please refer to the read across report in section 13.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritant / corrosive response data:

No test article-dependent findings were observed.

Other effects:

No toxic effects were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The test article was classified on the basis of the mean skin reactions at 24, 48 and 72 h after patch removal.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not a skin irritant.

Executive summary:

In a primary dermal irritation study performed according to OECD TG 404, 3 New Zealand White rabbits were dermally exposed to 0.5g calcium hydroxide (unchanged) to 6 cm²of skin surface. Test sites were covered with a semiocclusive dressing for 4 hours. Animals were the observed for 72 hours. Irritation was scored by the method of Draize.

There were no test article related irritative effects observed. No other adverse effects occured.

In this study, calcium hydroxide is not a dermal irritant.

According to the Regulation (EC) No. 1272/2008 and subsequent regulations, the test item is not a skin irritant.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

As calcium carbide instantly hydrolyses to Ca(OH)2 and C2H2 upon contact with water/moisture the assessment is based on the degradation products. For details please refer to the read across report in section 13.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: at 48-hour observation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: at 72-hour observation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: observation time

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: observation time

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: at 72-hour observation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: at Day 6

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: at Day 6

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: at Day 7

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: at Day 7

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: at Day 8

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: at Day 7

Irritant / corrosive response data:

Very slight to pronounced chemosis and red blotch of the conjunctiva (score 1 to 3) were observed in all animals until day 5.
As of 24 hours and for 48 to 96 hours, clear or purulent watering was noted. Inflammation of the iris (score 1) was observed at
24 hours in 2 animals. Slight to very slight corneal opacity, accompanied by inflammation of the iris (score 1), was observed as
of days 2 to 6 in the third rabbit. No corneal opacity was noted in one rabbit, and only very slight opacity was observed 24 and
48 hours after treatment in the remaining animal. In the rabbit without damage to the cornea, total reversibility of the eye
reactions was observed on day 6. in the rabbit with very slight corneal opacitiy, focal necrosis of the palebral conjunctiva was
observed from day 6 to day 13. As of day 9, purulent watering reappeared, and as of day 12 to 17, the lids had to be forced
open for observation. As of day 6 and for the rest of the study, slight to serious chemosis (score 2 to 4) accompanied by a
slight to pronounced red blotch of the conjunctiva (score 2 or 3) was noted; the conjunctival reactions were more pronounced
as of day 12 to 17. In the third animal, focal necrosis of the palebral conjunctiva was observed from day 4 to the end of the
study. White spots appeared on the cornea on day 7, and were still observed on day 22. All the other eye reactions
disappeared on day 8.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Under the experimental conditions, the product, 150 g/l calcium hydroxide, is considered as an irritant to the eye in rabbits.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is classified as Category 1.

Executive summary:

In a primary eye irritation study performed according to OECD TG 405, 0.1 ml of calcium hydroxide (150 g/l) was instilled

into the conjunctival sac of the left eye of 3 male New Zealand White rabbits. Eyes were not rinsed after administration of the test item. Animals were observed for 21 days. Irritation was scored by the method of Draize.

Very slight to pronounced chemosis and red blotch of the conjunctiva were observed in all animals until day 5.

As of 24 hours and for 48 to 96 hours, clear or purulent watering was noted. Inflammation of the iris was observed at 24 hours in 2 animals. Slight to very slight corneal opacity, accompanied by inflammation of the iris, was observed as of days 2 to 6 in the third rabbit. In the rabbit without damage to the cornea, total reversibility of the eye

reactions was observed on day 6. In the rabbit with very slight corneal opacitiy, focal necrosis of the palebral conjunctiva was observed from day 6 to day 13. As of day 9, purulent watering reappeared, and as of day 12 to 17, the lids had to be forced open for observation. As of day 6 and for the rest of the study, slight to serious chemosis accompanied by a slight to pronounced red blotch of the conjunctiva was noted; the conjunctival reactions were more pronounced as of day 12 to 17. In the third animal, focal necrosis of the palebral conjunctiva was observed from day 4 to the end of the study. White spots appeared on the cornea on day 7, and were still observed on day 22. All the other eye reactions disappeared on day 8.

Under the experimental conditions, calcium hydroxide, is considered as an irritant to the eye in rabbits.

According to Regulation (EC) No. 1272/2008 and subsequent regulations, the test item is classified as Eye Dam. Category 1.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

As calcium carbide instantly hydrolyses to Ca(OH)2 and C2H2 upon contact with water/moisture the assessment is based on the degradation products. For details please refer to the read across report in section 13.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 1 hour after administration

Score:

4

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other: Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons, and the product was not tested on the other 2 rabbits.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1 hour after administration

Score:

4

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other: Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons, and the product was not tested on the other 2 rabbits.

Irritant / corrosive response data:

Very severe eye reactions were observed 1 hour after the treatment, with pronounced chemosis (score:3), necrotised
appearance of the conjunctiva, whitish watering and total opacity of the cornea, showing nacreous appearance. The iris was
no longer visible.
Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons, and the product was
not tested on the other 2 rabbits.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Under the given experimental conditions, the product, calcium hydroxide, is considered as an irritant to the eye in rabbits.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is classified as Category 1.

Executive summary:

In a primary eye irritation study performed according to OECD TG 405, 100 mg of calcium hydroxide as such were instilled into the conjunctival sac of the left eye of one male New Zealand White rabbit. The eye was not rinsed after administration of the test item. The animal was observed for 21 days. Irritation was scored by the method of Draize.

Very severe eye reactions were observed 1 hour after the treatment, with pronounced chemosis (score:3), necrotised appearance of the conjunctiva, whitish watering and total opacity of the cornea, showing nacreous appearance. The iris was no longer visible.

Given the seriousness of the eye lesions observed, the animal was put down for humanitarian reasons, and the product was not tested on the other 2 rabbits.

Under the experimental conditions, calcium hydroxide, is considered as an irritant to the eye in rabbits.

According to Regulation (EC) No. 1272/2008 and subsequent regulations, the test item is classified as Eye Dam. Category 1.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

In aqueous solution, calcium carbide (CaC2) rapidly decomposes into calcium hydroxide (Ca(OH)2) and acetylene (C2H2). Local effects are related to calcium hydroxide, which liberates OH- ions, affecting the skin and the mucous membranes. C2H2 is released as a gas and is not expected to contribute to the local effect.

Skin: Calcium hydroxide has been tested as "not irritating to the skin" in rabbits when applied as a dry powder (Bien 1994, OECD 404), and as "irritating" when applied in putty form (Vaeth 2004).

The pH of 1 % calcium carbide (w/w) in water is 12.48. According to REACH Annex VIII, this pH could be used for classification of CaC2 as corrosive. However, determination of the alkali reserve (Möller, 2011) indicated that CaC2 is not corrosive based on a alkali reserve value of 14.5. This conclusion is supported by in vivo studies in rabbits (OECD 404). Skin irritation, but not corrosivity, was also observed in the acute dermal toxicity study (Kietzmann 1994).

Eye: Calcium hydroxide has been tested as "irritating to the eye" (de Jouffrey, 1995). This classification is supported by several case reports (i.e. Testud, 2002).

Respiratory irritation: Calcium oxide evokes irritating chemaesthesis at exposures in the range of 2 to 5 mg/m³ (Cain 2004). Due to the fact that in contact with water CaO forms Ca(OH)2 , the result can be used to predict the respiratory irritation properties of CaC2 (which also forms Ca(OH)2 in contact with water).

Justification for selection of skin irritation / corrosion endpoint:
GLP guideline study with calcium hydroxide

Justification for selection of eye irritation endpoint:
GLP guideline study with calcium hydroxide

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: highly irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

The results of pH evaluation of calcium carbide in water suggest that classification as corrosive should be considered. However, based on an assessment of the alkali reserve and in vivo studies using Ca(OH)2 classification as "irritating to the skin" is warranted.

Data from in vivo eye irritation studies in the rabbit show that calcium dihydroxide caused irreversible lesions in the eye.

Data are available that indicate that calcium dihydroxide is irritating to the respiratory tract.

The high pH (12.48) for 1 % calcium carbide in water results from formation of calcium dihydroxide by hydrolysis of calcium carbide,and from the impurity calcium oxide. It is therefore considered that read-across of the experimental results from calcium dihydroxide and calcium oxide to calcium carbide is appropriate. These results supersede classification on the basis of pH.

Based on experimental results on the decomposition products, calcium carbide requires classification as follows:

Skin Irrit 2 (H315 – Causes skin irritation)

Eye Damage 1 (H318 - Causes serious eye damage)

STOT SE 3 (H335 - May cause respiratory irritation)