Paraffin waxes (Fischer-Tropsch), isomerization

Endpoint summary

Description of key information

Acute oral toxicity

- OECD 420 (fixed dose method; GLP), test item GTL waxy raffinate (C15-50; CAS 848301-87-1, EC 482-130-1): LD₅₀ in female Sprague-Dawley strain rat was estimated to be greater than 5000 mg/kg bodyweight;

- OECD 420 (fixed dose method; GLP), test item GTL base oil (C18-50; CAS 848301-69-9, EC 482-220-0): LD₅₀ in female Sprague-Dawley strain rat was estimated to be greater than 5000 mg/kg bodyweight.

- Supporting data on further closely related substances confirm the low oral toxicity: in the three available studies, the LD₅₀ in rats was also estimated to be greater than 5000 mg/kg body weight.

 

Acute inhalation toxicity

Taking into account the very low vapour pressure of the registration substance, exposure via the inhalation route is unlikely and it is therefore considered justified to omit this endpoint information.

Supporting data on the closely related substance GTL base oil 4 (covering the range, ~C18-41) indicate the low inhalation toxicity.

 

Acute dermal toxicity

OECD 402 (fixed dose method; GLP), test item GTL base oil (C18-50; CAS 848301-69-9, EC 482-220-0): LD₅₀ in male and female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Supporting data on further closely related substances confirm the low dermal toxicity: in the two available studies, the LD₅₀ in rats was estimated to be more than 2000 mg/kg body weight and more than 3600 mg/kg body weight, respectively.

 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

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

Remarks:

read-across from closely related Gas-to-liquids (GTL) product [covering the low molecular weight fraction of the registration substance, C18-50]

Adequacy of study:

key study

Justification for type of information:

justification for analogue approach: see IUCLID section 13 "Read-across justification"

Reason / purpose for cross-reference:

read-across source

Preliminary study:

No signs of systemic toxicity noted (single animal at 5000 mg/kg).

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Remarks on result:

other: No 95% CL stated

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

None

Individual Clinical Observations and Mortality Data

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
5000	1-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

 

Individual Bodyweights and Bodyweight Changes

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
5000	1-0 Female	228	256	273	28	17
	2-0 Female	225	253	289	28	36
	2-1 Female	218	240	280	22	40
	2-2 Female	223	259	289	36	30
	2-3 Female	215	249	262	34	13

 

Individual Necropsy Findings

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
5000	1-0 Female	Killed Day 14	No abnormalities detected
	2-0 Female	Killed Day 14	No abnormalities detected
	2-1 Female	Killed Day 14	No abnormalities detected
	2-2 Female	Killed Day 14	No abnormalities detected
	2-3 Female	Killed Day 14	No abnormalities detected

0= No signs of systemic toxicity

Interpretation of results:

other: EU-GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test material GTL waxy raffinate (CAS 848301-87-1, EC 482-130-1) in the female Sprague Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight.

Executive summary:

Introduction. The study was performed to assess the acute oral toxicity of the test material GTL waxy raffinate (C15-50; CAS 848301-87-1, EC 482-130-1) in the Sprague‑Dawley CD strain rat. The method was designed to meet the requirements of the following:

- OECD Guidelines for Testing of Chemicals No 420 “Acute Oral Toxicity - Fixed Dose Method” (adopted)

- Method B.1 bis Acute Toxicity (Oral) of Commission Directive 2004/73/EC.

Method. Following a preliminary test in which there was no death at a dose level of 5000 mg/kg, an additional four fasted female animals were given a single oral dose of undiluted test material at a dose level of 5000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Bodyweight. All animals showed expected gains in bodyweight.

Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute oral median lethal dose (LD₅₀) of the test material GTL waxy raffinate in the female Sprague‑Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight (Globally Harmonised Classification System-Unclassified).

 

Since oral absorption decreases with increasing carbon chain length/molecule size and virtually no absorption occurs at >C50, it can be safely concluded that the results of this test item (covering the entire low molecular weight fraction of the registration substance up to C50) should also apply to the registration substance containing higher molecular weight constituents (C25-150, approx. 30-55 % >C50).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Remarks:

read-across from closely related Gas-to-liquids (GTL) product [covering the low molecular weight fraction of the registration substance, C18-50]

Adequacy of study:

key study

Justification for type of information:

justification for analogue approach: see IUCLID section 13 "Read-across justification"

Reason / purpose for cross-reference:

read-across source

Preliminary study:

There was no death and no signs of systemic toxicity at 5000 mg/kg.
In the absence of toxicity at 5000 mg/kg, an additional group of 4 animals was treated at a dose level of 5000 mg/kg.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

other: EU-GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight.

Executive summary:

Introduction. The study was performed to assess the acute oral toxicity of the test material GTL base oil (C18-50; CAS 848301-69-9, EC 482-220-0) in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of the following:

• OECD Guidelines for Testing of Chemicals No 420 "Acute Oral Toxicity - Fixed Dose Method" (adopted 17 December 2001)

• Method B1 bis Acute Toxicity (Oral) of Commission Directive 2004/73/EC Method.

Method. Following a preliminary test in which there was no death at a dose level of 5000 mg/kg, an additional four fasted female animals were given a single oral dose of undiluted test material at a dose level of 5000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Bodyweight. All animals showed expected gains in bodyweight.

Necropsy. No abnormalities were noted at necropsy.

 

Conclusion. The acute oral median lethal dose (LD₅₀) of the test material GTL base oil in the female Sprague-Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight (Globally Harmonised Classification System - Unclassified).

 

Since oral absorption decreases with increasing carbon chain length/molecule size and virtually no absorption occurs at >C50, it can be safely concluded that the results of this test item (covering the entire low molecular weight fraction of the registration substance up to C50) should also apply to the registration substance containing higher molecular weight constituents (C25-150, approx. 30-55 % >C50).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Remarks:

read-across from closely related Gas-to-liquids (GTL) product [covering the low molecular weight fraction of the registration substance, C18-50]

Adequacy of study:

key study

Justification for type of information:

justification for analogue approach: see IUCLID section 13 "Read-across justification"

Reason / purpose for cross-reference:

read-across source

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: 10 % of the total body surface area
- Type of wrap if used: surgical gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hout exposure period the area was wiped with cotton wool moistened with arachis oil BP
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume or concentration used: yes; 2.48 mL/kg

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities occured.

Clinical signs:

other: No signs of systemic toxicity were observed.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Slight desquamation was observed in 3 females on days 4, 5 and 6 of the 14-day study period.

Interpretation of results:

other: EU-GHS criteria not met

Conclusions:

LD50 > 2000 mg/kg bw

Executive summary:

An acute dermal toxicity study for GTL base oil (C18-50; CAS 848301-69-9, EC 482-220-0) was performed to assess the acute dermal toxicity in rat. The study was conducted according to OECD TG 402, and in compliance with GLP.

A single dose of 2000 mg/kg bw of undiluted test material was applied onto the skin of 5 male and 5 female rats. The test item was held in contact with the skin under semi-occluded dressing for 24 hours. Observations for clinical signs of toxicity were performed at 30 min, 1, 2, and 4 hours post-application and every day for the 14 day study period. Body weights were recorded prior to the treatment and at days 7 and 14. At the end of the study the tested animals were killed by cervical dislocation. External examination and opening of the abdominal and thoracic cavities were performed at necropsy. Behavioural and clinical observations, gross lesions, body weight changes, mortality and any other toxicological effects were noted during the 14 day study period. The test sites were examined for evidence of primary irritation and scored.

No mortalities occured at during the 14 -day study period. There were no signs of systemic toxicity. All females showed no body loss or gain in body weight during the first week and expected gain in body weight in the second week. The males showed expected gain in body weight during the 14 day study period. No abnormalities were noted at necropsy.

The LD₅₀ value for GTL base oil (C18-50; CAS 848301-69-9, EC 482-220-0) was concluded to be > 2000 mg/kg bw. It is expected that the results of this test item (covering the entire low molecular weight fraction of the registration substance up to C50) should also apply to the registration substance containing higher molecular weight constituents (C25-150, approx. 30-55 % >C50). However, as current regulatory consensus is that hydrocarbons with carbon chain lengths of >C20 are not considered systemically available via the cutaneous exposure route (Petry et al., 2017). For the target substance with carbon numbers C25 and above, dermal exposure is not considered relevant.

Reference 

Petry, T., Bury, D., Fautz, R., Hauser, M., Huber, B., Markowetz, A., ... & Teichert, T. (2017). Review of data on the dermal penetration of mineral oils and waxes used in cosmetic applications. Toxicology letters, 280, 70-78.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

All of the available studies indicate that acute toxicity is low with no observed mortalities.

Since hydrocarbons with carbon numbers greater than C35 are not orally absorbed to a significant extent and because hydrocarbons with carbon chain lengths of >C20 are not considered systemically available via the cutaneous exposure route (see toxicokinetic section), it is considered justified to use the data of the closely related substances GTL base oil and GTL waxy raffinate, both covering the entire low molecular weight fraction of the registration substance up to C35 and beyond (up to C50).

Based on the results of these two substances, the LD₅₀ of the registration substance 'Paraffin waxes (Fischer-Tropsch), isomerization' is considered to be >5000 mg/kg bw in female rats via the oral route and >2000 mg/kg bw in male and female rats via the dermal route. 

Generally, since the registration substance contains components with a high carbon number (C25-150), it can be assumed that only a small proportion of the components in the lower carbon number range can be absorbed orally. The dermal absorption and the absorption by inhalation can be considered negligible.

 

Justification for classification or non-classification

Based on reliable data from closely related substances, no classification for lethal effects following a single exposure is required for the registration substance 'Paraffin waxes (Fischer-Tropsch), isomerization' (according to Regulation 1272/2008/EC).