Potassium 3-sulphopropyl methacrylate

Endpoint summary

Description of key information

Acute toxicity oral: Acute study oral (gavage), rat (Wistar) m/f (OECD 401, GLP): LD50 > 5000 mg/kg, LD0 >= 5000 mg/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 January - 12 February 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

under GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted May 12, 1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

EWG Directive 84/449/EWG, Amtsblatt der Europaeischen Gemeinschaften L 251, Jahrgang 27, 19.9.84, B.1. Akute Toxizitaet - oral /96

Deviations:

no

GLP compliance:

yes

Remarks:

The study was performed in compliance with OECD Principles of Good Laboratory Practice (see Bundesanzeiger Nr. 42a, 2nd March 1983, FRG).

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: KFM-Han. Wistar (outbred, SPF-Quality)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG , 4414 Fuellinsdorf , Switzerland
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: males : 234-294 g , females : 184-210 g
- Fasting period before study: 12-18 hours before treatment , approximately 1 hour after treatment
- Housing: animals were caged in groups of five in Macrolon cages type 3 with standard softwood bedding
- Diet (e.g. ad libitum): pelleted standard Kliba 343 , Batch 36/85 rat maintenance diet , ad libitum
- Water (e.g. ad libitum): tap water , ad libitum
- Acclimation period: 1 week under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40-70
- Air changes (per hr): 14-15
- Photoperiod (hrs dark / hrs light): 12/12

IDENTIFICATION: by unique cage number and corresponding colour-coded spots
RANDOMIZATION: animals were randomly selected at time of delivery in groups of five.

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

4% solution of CMC in distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle : 4% solution of CMC, carboxymethylcellulose sodium salt purum (Fluka AG) in distilled water
- Amount of vehicle (if gavage): Group 1 : 10 ml at 1000 mg/kg ; Group 2 : 20 ml at 5000 mg/kg

MAXIMUM DOSE VOLUME APPLIED : 20 ml at 5000 mg/kg

DOSAGE PREPARATION (if unusual):
The test article was placed into a glass beaker an a tared Mettler PK 4800 balance, and the vehicle (4 % solution of CMC, carboxymethylcellulose sodium salt purum, Fluka AG, CH 9470 Buchs / Switzerland in distilled water) was added. A weight by volume dilution was prepared using a homogenizer (Ultra-Turrax, Janke and Kunkel, Staufen, FRG).Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer (Auer-Bittmann, Switzerland) . The preparation was made immediately prior to dosing.

Doses:

1000 mg/kg bw and 5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 15 days

- Frequency of observations and weighing:
Mortality : Four times during test day 1, and daily during days 2-15
Body weight : Test days 1 (pre-administration) , 8 and 15
Symptoms : Each animal was examined for changes in appearance and behaviour four times during day 1, and daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed : All animals were necropsied . All animals were killed by intraperitoneal injection of sodium pentobarbitone.


- Other examinations performed: other:
The animals were checked for the symptoms listed below .
- General behaviour : aggressive,crying,restlessness/excitation,nervousness,fear,sedation,somnolence,sleep,coma
- Respiration : apnea,dyspnea,rales
- Eye : chromodacryorrhea,exophthalmos,miosis,mydriasis,whitish discharge,lid adhesion,lacrimation
- Nose : rhinorrhea,epistaxis
- Motility : akinesia,ataxia,drooped head,hyperkinesia,hypokinesia,paralysis flaccid,paralysis spatic,paddling movements,stiff movements,rolling movements,hunched posture
- Body posture : ventral body position,latero-abdominal position,curved body position
- Skin : erythema,edema,necrosis
- Motor susceptibility : spasms,tonic muscle spasms,clonic muscle spasms,opisthotonus,saltatory spasms,trismus,retching,"Straub" phenomenon,tremor,muscle -twitching
- Various : loss of weight,emaciation,negative corneal reflex,diarrhea,ruffled fur,necrosis of tissue of application area,salivation,pallor,cyanosis

Statistics:

The LOGIT-Model could not be applied to the observed rates of death. The toxicity was estimated without use of a statistical model.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

Clinical signs were noted, but no mortality

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

clinical signs were noted, but no mortality

Mortality:

Males and females :
0% at 1000 mg/kg
0% at 5000 mg/kg

Clinical signs:

other: The following symptoms were observed : 1000 mg/kg : sedation,dyspnea 5000 mg/kg : sedation,dyspnea,diarrhea All rats had recovered within 3 hours to 3 days after test articIe treatment.

Gross pathology:

No macroscopic organ changes were observed in the animals.

Interpretation of results:

GHS criteria not met

Remarks:

LD50 > 5000 mg/kg

Conclusions:

The study was performed according to the OECD TG401 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1) and so sufficiently reliable to assess the acute oral toxicity of the test item to rats. The test material did not induce mortality up to the highest tested dose of 5000 mg/kg. The test material was hence considered to be non-toxic under the conditions of the test and not requiring classification according to Regulation (EC) 1272/2008.

Executive summary:

The acute oral toxicity of the test material was investigated in rats. The test was conducted according to OECD TG401. As doses 1000 and 5000 mg/kg bw of the test substance were administered via gavage to the rats. Observations were made for a period of 15 days. No mortalities or signs of systemic toxicity, besides sedation and dyspnea in the 1000 mg/kg bw group and sedation,dyspnea and diarrhea in the 5000 mg/kg bw group respectively. The animals had recovered within 3 hours to 3 days after administration. No treatment-related body weight changes were reported. No pathological abnormalities were found in any of the treated animals. The acute oral medium lethal dose (LD50) of the test material in rats of both sexes observed over a period of 15 days was estimated to be greater than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

There is a OECD 401 study under GLP available, assessed with Klimisch 1, hence, the database is of high quality.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to REACH Annex VIII column 2, testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.
The test substance is a white, odourless powder (at 20°C and 1013 hPa). The test material changes after start of melting at 254°C into decomposition at >300°C, and has also a very low vapour pressure (1.05 * 10exp(-9) Pa, calculated). So, the exposure to potassium 3-sulphopropyl methacrylate (SPM) via inhalation of vapour can be disregarded as no vapour will be formed during handling.
The substance, however, has intrinsically a particle size which needs to be regarded. According to ECHA’s guidance R.7a Endpoint specific guidance Version 5.0 – December 2016, particles with a size <100µm belong to the inhalable fraction, <10µm to the thoracic fraction, and <4µm to the respirable fraction. The relevant values for particle size distribution are: D (0.10): 1.82 µm; D (0.25): 4.08 µm, D (0.50): 9.05 µm, D (0.55): 10.54 µm, D (0.90): 64.58 μm, D (0.95): 121.58 µm
This results in the following fractions according to the given limit values:~ 90-95% are <100 µm (inhalable fraction), ~ 50-55% are <10 µm (thoracic fraction), and ~ 25% are < 4µm (respirable fraction). So theoretically, the inhalative route, which does not allow an assessment of the systemic toxicity as well as via the oral route, may also be relevant for humans. In the present case, however, it is not. All identified process categories indicate no likelihood of exposure, i.e. Use in closed process, no likelihood of exposure, all transfer is done in dedicated vessels or filling lines.
Furthermore, testing is scientifically not necessary and would not reveal any additional information which cannot be derived from other available acute toxicity data, so that testing can be omitted due to animal welfare:
According to ECHA’s guidance, moderate log P values (between -1 and 4) are favourable for absorption directly across the respiratory tract epithelium by passive diffusion. The log Pow of SPM was estimated as -3.1 (KOWWIN (v1.68)). Hence, this value indicates a very low potential for absorption, which is supported by a water solubility of 2570 g/l at 23°C. Consequently, absorption here is hindered. Further, the available oral toxicity study indicates a very low toxicity of SPM. The LD50 via the oral route could not be determined as no mortality was observed up to the top dose of 5000 mg/kg, only clinical signs were observed: At 1000 mg/kg, sedation,dyspnea, at 5000 mg/kg, sedation, dyspnea, and diarrhea were noted. All rats had recovered within 3 hours to 3 days after test item treatment.
There is no study available and also not required for the acute inhalation toxicity of SPM, as the relevant information can be drawn from the acute oral LD50 of >5000 mg/kg and estimation of the absorption of the test item via both routes.
According to OECD guideline 403 (Acute inhalation toxicity), the concentration of respirable particles for limit testing is 5 mg/L over 4 h. Taking into account for rats a standard respiratory volume of 0.2 l/min and average body weight of 250 g (Guidance on information and requirements and chemical safety assessment, chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, November 2012, ECHA, http://echa.europa.eu/web/guest/guidance-documents/guidance-on-information-requirements-and-chemical-safety-assessment), a total respiratory volume of 48 litre over 4 h can be assumed. This would result in a total dose of 240 mg per rat, which is equivalent to 960 mg/kg bw.
Assuming in a worst-case scenario, which is rather unrealistic, that this total dose will be absorbed to 100%, and assuming furthermore that the orally applied amount is only absorbed to 50%, this dose would correspond to an oral dose of 1920 mg/kg bw. This value is below the relevant determined LD50 and even LD0 via the oral route, i.e. >5000 mg/kg bw. Hence, it can be reasonably assumed that an additional acute toxicity test via the inhalation route would reveal an LC50inhalation >5 mg/l, most likely even a LC0inhalation ≥5 mg/l. This is supported by the reasonably assumable at least partially hindered absorption via the inhalatory route compared to the oral one.
Furthermore, SPM is neither a skin nor eye irritant. So it can be additionally concluded, that no local effects during inhalation toxicity testing are likely occur and need to be regarded.
In consequence, the available oral acute toxicity study is sufficient to cover this endpoint, no acute toxicity testing via inhalation route needs to be performed and can consequently be waived due to animal welfare.

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to the later amendment of REACH, i.e. Commission Regulation (EU) 2016/863 of 31 May 2016, testing by the dermal route does not need to be conducted if:
— the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and
— no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation) or, in the absence of an in vivo study by the oral route, no systemic effects after dermal exposure are predicted on the basis of non-testing approaches (e.g. read across, QSAR studies).
The oral LD50 in rats is >5000 mg/kg, no animal died at 5000 mg/kg, clinical signs were sedation, dyspnea, diarrhea, and all rats had recovered within 3 hours to 3 days after test articIe treatment. No clinical signs were noted at both skin irritation (registered substance SPM) and sensitization (read-across substance SPA) testing. Hence, testing can be waived.

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available oral toxicity values are LD50 > 5000 mg/kg, LD0 >= 5000 mg/kg, which is way beyond the limit value for classification of 2000 mg/kg as demanded by Regulation 1272/2008. Hence, no classification is triggered.