Paracetamol

Endpoint summary

Description of key information

The substance Paracetamol  was found to be irritating in skin and eye category.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Skin irritation toxicity of acetaminophen (paracetamol)on rats

GLP compliance:

not specified

Species:

rat

Strain:

Fischer 344

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Charles River Inc., Atsugi, Japan
- Age at study initiation:6 weeks
- Weight at study initiation:
- Diet (e.g. ad libitum):basal diet (Oriental M, Oriental Yeast Co., Tokyo)
- Water (e.g. ad libitum):tap water ad libitum

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not specified

Duration of treatment / exposure:

week 32

Number of animals:

40 animals ,four groups (five rats each)

Irritation parameter:

overall irritation score

Basis:

mean

Reversibility:

no data

Remarks on result:

other: Skin rashes have been reported

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The paracetamol (acetaminophen) caused minimal irritation in rats at a concentration of 1.3%.,Skin rashes have been reported by paracetamol.

Executive summary:

The paracetamol (acetaminophen) caused minimal irritation in rats at a concentration of 1.3%.,Skin rashes have been reported by paracetamol.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.1

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Vehicle:

not specified

Controls:

not specified

Duration of treatment / exposure:

1  days

Number of animals or in vitro replicates:

6

Irritation parameter:

other: MMAS(modified maximum average score (MMAS))

Basis:

mean

Time point:

other: 1 d

Score:

30.8

Reversibility:

not specified

Remarks on result:

other: Irritation observed

The prediction was based on dataset comprised from the following descriptors: MMAS
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((("a" or "b" or "c" or "d" or "e" or "f" )  and ("g" and ( not "h") )  )  and "i" )  and ("j" and "k" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Phenols (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Carboxamide AND Phenol AND Precursors quinoid compounds by Organic functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Carboxamide AND Overlapping groups AND Precursors quinoid compounds by Organic functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Amide, aliphatic attach [-C(=O)N] AND Aromatic Carbon [C] AND Carbonyl, aliphatic attach [-C(=O)-] AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound AND Carbonic acid derivative AND Carboxylic acid amide AND Carboxylic acid derivative AND Carboxylic acid sec. amide AND Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.1

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> N-acylamides OR Acylation >> Direct acylation involving a leaving group >> N-acylsulphonamides by Protein binding by OASIS v1.1

Domain logical expression index: "i"

Similarity boundary:Target: c1(O)ccc(NC(C)=O)cc1
Threshold=10%,
Dice(Atom centered fragments)

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.99

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.05

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

By the modified maximum average score (MMAS) from QSAR eye irritation score of Paracetamol is estimated as 30.8. This score indicates that Paracetamol is irritating to the eyes of rabbit.(as the criteria MMAS ≤ 59 is irritating).

Executive summary:

By the modified maximum average score (MMAS) from QSAR eye irritation score of Paracetamol is estimated as 30.8. This score indicates that Paracetamol is irritating to the eyes of rabbit.(as the criteria MMAS ≤ 59 is irritating).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

No. of studies were reviewed for skin irritation from reliable sources having Klimisch rating 2 .

The summary of the results are presented below

By applying weight of evidence approach to the target substance Paracetamol ,it is concluded that the substance is irritating to the eyes of rabbit and mouse.

Minimal irritation was observed after administration of 1.3% acetaminophen as reportgiven by Tsuca et.al (Carcinogenesis (London) 1988, 9(4), 547-554).Similarly the QSAR prediction estimated the irritation score to be 1.78% indicating it to be skin irritant

 

By applying weight of evidence approach to the target substance Paracetamol,it is concluded that the substance is irritating to the skin of rabbit.

Eye irritation

No. of studies were reviewed for eye irritation from reliable sources having Klimisch rating 2 and 4.

The summary of the results are presented below

 

Sr.No	Irritation Parameter	Interpretation of results	Species	Sources
1	MMAS(modified maximum average score (MMAS))	Irritating	Rabbit	Predicted data from QSAR
2	Overall irritation score	Irritating	Mouse	Handbook data
3	Overall irritation score	Moderately Irritating	Rabbit	Publication data for Read across

 

By applying weight of evidence approach to the target substance Paracetamol ,it is concluded that the substance is irritating to the eyes of rabbit and mouse

Justification for selection of skin irritation / corrosion endpoint:

The paracetamol (acetaminophen) caused minimal irritation in rats at a concentration of 1.3%.,Skin rashes have been reported by paracetamol.

Justification for selection of eye irritation endpoint:

By the modified maximum average score (MMAS) from QSAR eye irritation score of Paracetamol is estimated as 30.8. This score indicates that Paracetamol is irritating to the eyes of rabbit.(as the criteria MMAS ≤ 59 is irritating).

Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

The available studies indicate that the substance Paracetamol is classified as a skin and eye irritant according to CLP regulation.