Registration Dossier

Administrative data

Description of key information

No indication for acute oral or acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
July 29, 1998 - September 07, 1998
Reliability:
2 (reliable with restrictions)
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: aqueous solution
Doses:
2000 mg/kgbw
No. of animals per sex per dose:
5 males
5 females
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw

A single dose of the aqueous solution (6 g ad. 30 ml) was administered after an overnight fasting by oral gavage, using a metal catheter and disposable plastic syrings, with a constant volume of 1 ml/100 gbw to each of 5 males and 5 females. Individual doses were adjusted according to the body weight on the day of administration.

No animal died after single oral administration of 2000 mg/kgbw of BRUGGOLITE FF6. The LD50 rat is > 2000 mg/kgbw

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

Guidance on information requirements and chemical safety assessment, Chapter R.7a, p.279: Endpoint specific guidance, Guidance for the implementation of REACH, May 2008, ECHA:

Non-testing data can be provided by grouping methods. Practically, BRÜGGOLITE FF6 is devoid of any acute oral toxicity. Due to the structural similarity between the main component of BRÜGGOLITE FF6 and BLANCOLEN HP, read across can be applied.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
satisfying

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02/0215 to 04/2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
Sample Name: FA8
Batch: 14102401
Supplier: Brüggemann Chemical, L. Brüggemann KG
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Supplier: Charles River C/Argenters 7, Local AB 08290 Cerdanyola del Vallés Barcelona – Spain.
Health status: Specific Pathogen Free (SPF).
Rationale for selection of species / strain: The Sprague Dawley rat is a suitable rodent strain, acceptable to regulatory authorities as a recommended rodent test system, and for which extensive background data are available.
Total number of animals: 8: 6 used in the study (3 males and 3 females, allocated to first dose level (5.16 mg/mL) and 2 spare animals.
Age of the animals at exposure: 8 weeks
Animals per cage (before / after distribution): 4 (before distribution), 3 (after distribution)
Bedding material: Capsumlab Lecho_10 (autoclavable)
Change of cages: Once a week.
Inclusion criteria on arrival: Veterinary inspection.
Acclimatisation period: 8 days.
Animal identification: Digit ink marks.

Light cycle: 12:12, 07.00 to 19.00 CET
Pressure gradient: Animal holding room positive to corridors
Temperature: 18.6-23.5ºC
Relative humidity: 20-47%

Food: Global Diet
Reference: 2914 C
Supplier: Harlan Teklad Station Road Blackthorn, Bicester Oxon, OX25 1TP United Kingdom
Nutritional and contaminant contents:Certificate of analysis for the batch used is included in annex II
Food availability: Ad libitum, except when animals were restrained in the exposure tubes
Drinking water: Tap Water
Watering: Bottles
Quality control: Certificate of analysis is included in annex III
Water availability: Ad libitum, except when animals were restrained in the exposure tubes
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
> 1 - < 4 µm
Geometric standard deviation (GSD):
> 1.5 - < 3
Details on inhalation exposure:
Inhalation exposure was performed using a flow-past, nose-only exposure system. The animals were confined separately in restraint tubes which were positioned radially around the exposure chamber. The exposure system ensured a uniform distribution and provided a constant flow of test material to each exposure tube. The flow of air at each tube was approximately 1 L/min, which was sufficient to minimize re-breathing of the test aerosol as it is more than twice the respiratory minute volume of rats.
Exposure chambers type EC-FPC-232 (anodised aluminium, volume inside compartment: approximately 3 L), equipped with glass exposure tubes were used. The rats were individually exposed in glass tubes matching their size. Before treatment start the homogeneity for the different levels of the exposure chamber was confirmed. Cross and longitudinal sections of the chamber are shown in Figure 1.
The temperature and relative humidity of the test atmosphere in the exposure chamber was maintained as required by experimental conditions. Air flow was monitored regularly.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric
Duration of exposure:
4 h
Concentrations:
5.16 mg/l
No. of animals per sex per dose:
3 males, 3 females
Control animals:
no
Details on study design:
The test was based on a stepwise procedure. The starting dose (5 mg/L air, during 4 hours) was selected since the test item was expected to be non-toxic according to previous studies conducted by sponsor. No additional doses were required.

3 male and 3 female rats in group A (starting dose group) were exposed for 4 consecutive hours.
During an observation period of 14 days, clinical observations and body weight were collected in order to characterise the toxicological effects of the aerosol. All animals were subjected to a gross necropsy and descriptions of all macroscopic abnormalities were recorded.

Acclimatisation to the nose-only restraining tubes was performed for approximately 80 minutes immediately before the exposure.
Statistics:
No statistical analysis was performed.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.16 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
none
Clinical signs:
other: Dirty fur, chromorrhinorrhea, chromodacryorrhea and piloerection were observed in all animals immediately after administration and 1 hour after exposure. These clinical signs were not longer present on day 2 of study and no other clinical signs were obser
Body weight:
A slight decrease in body weight (approximately 1-2% less than body weight at pre-treatment) was observed in all animals from day 1 of study to day 2 of study. Males recovered the body weight at pre-treatment at day 3 of study. Thereafter, a normal body weight gain was observed in males. By contrast, a stagnation of body weight was observed in females, which did not recover the body weight at pre-treatment until day 6 of study. Females gained weight normally from day of study 6 onwards.
Gross pathology:
No macroscopic findings were observed during necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
No classification according to (EU) No. 1272/2008 required.
Executive summary:

Treatment of Sprague Dawley rats with the test item resulted in no deaths. Clinical signs were considered to be mainly stress related to the nose-only exposure but a contribution of the treatment with the test item cannot be completely excluded. Additionally, body weight stagnation in females is considered to be related with the test item.

It is concluded that, under the experimental conditions:

- LC50 of the test item was greater than 5.16 mg/L air (gravimetric aerosol concentration)

- Based on the GHS classification criteria, the test item can be considered as not classified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 160 mg/m³
Quality of whole database:
satisfying

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
November 1998 - January 1999
Reliability:
2 (reliable with restrictions)
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
other: rat, Wistar Crl:WI BR
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH
- Age at study initiation: 35-42 days
- mean body weight at study initiation:
males: 291.8 g +/- 9.8 g, n=5
females: 199.8 g +/- 3.1 g; n=5
- Fasting period before study:
- Housing: Altromin Type S8/15, granulated soft wood bedding
- Diet (ad libitum): Altromin 1326, pelleted standard diet, Batch# 150299/1351
- Water (ad libitum): tap water (municipal supply)
- Acclimation period: 13 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22.5°C
- Humidity (%): 45-70%
- Air changes (per hr): air conditioned.
- Photoperiod (hrs dark / hrs light): artificial light was set to give a cycle of 12 our light and 12 hours dark, the light phase was from
6.30 a.m. - 6.30 p.m.
Type of coverage:
occlusive
Vehicle:
water
Remarks:
distilled water
Details on dermal exposure:
TEST SITE
- Area of exposure: 6 x 6 cm (trunk)
- Type of wrap if used: covered with aluminium foil (6.5 x 6.5 cm) which was fixed in place with sticking plaster (Lohmann GmbH & Co, Neuwied)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the application area was washed with water
- Time after start of exposure: 24 hours after application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.2 g test item/ 100 g body weight. Individual doses were adjusted according to body weight on the day of administration

VEHICLE
- Amount(s) applied (volume or weight with unit): the gauze patch was moistened with distilled water
Duration of exposure:
24 h
Doses:
Dose group: 2000 mg/kg body weight (b.w.)
0.2 g of the test article per 100 g body weight were applied
No. of animals per sex per dose:
5 males per dose
5 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortality and morbidity continuously on the day of administration and once daily thereafter (in the morning). Animals were also observed for erythema and /or oedema at the skin of the application area one hour after patch removal and once daily thereafter (in the morning). Body weights were recorded on the day of administration and on days 7 and 14.
- Necropsy of survivors performed: At the end of the observation all animals were killed by CO2 inhalation. All animal swree examined externally. The cranial, thoracic and abdominal cavities were then opened and examined marcorscopically.
Statistics:
body weights: Calculation of group mean values and standard deviations.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No animal died during the course of investigation.
Male: > 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: > 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Clinical observations: No clinical signs were observed during the cours of investigation.
Body weight:
The body weight gain of the male and female animals was in the renage of th historical control data in the test facility.
Gross pathology:
There were no macroscopic pathological findings in the animals.
Other findings:
Skin of the application area: The skin of the application area was not altered.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item is neither a toxic nor a harmful substance according to this acute dermal toxicity study.
Executive summary:

Guidance on information requirements and chemical safety assessment, Chapter R.7a, p.279: Endpoint specific guidance, Guidance for the implementation of REACH, May 2008, ECHA:

Non-testing data can be provided by read-across method.

Important considerations for this read-across approach is:

 ·      BLANCOLEN HP shows very similar physico-chemical properties as BRUGGOLITE FF6

 ·      BLANCOLEN HP is a constituent of BRUGGOLITE FF6

 ·      The structural similarity between the two chemicals.

 ·      The oxidation of sufinate into sulfonate in aqueous solution

 

Acute dermal toxicity of BRUGGOLITE FF6 was tested on five female and five male rats. The test item was applied at a single dose of 2000 mg/kgbwto a shaved dorsal area of the animals’ trunk and then covered with a gauze patch which was held in contact with the skin with an occlusive dressing. Exposure time was 24 h. Then the affected area was washed with water. Animals were examined for mortality, clinical signs, alterations of the application area, body weight gain and pathological alterations of organs at the end of a 14-day observation period. None of the animals died during the course of the investigation. Clinical signs, skin alterations on the application area or pathological findings at necropsy could not be observed. The body weight gain was not affected.

Dermal LD50(rat) > 2000 mg/kgbw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
satisfying

Additional information

Due to the similarity and the test results obtained from BRUGGOLITE FF6, there is neither an indication for acute oral nor acute dermal nor acute inhalative toxicity potential of BLANCOLEN HP.

Acute oral toxicity of BRUGGOLITE FF6 was tested on rats at a single dose of 2000 mg/kgbw by gavage. None of the animals died during the course of investigation. No pathological findings were observed at necropsy. The body weight gain was not affected. LD50 oral> 2000 mg/kgbw

Acute dermal toxicity of BRUGGOLITE FF6 was tested with rats. The substance was applied at a single dose of 2000 mg/kgbw to a shaved dorsal area of the trunk of the animals. Exposure was for 24 hours. None of the animals died during the course of the investigation. Clinical signs, skin alterations on the application area or pathological findings at necropsy were not observed. The body weight gain was not affected.
LD50 dermal> 2000 mg/kgbw

Acute inhalative toxicity of BLANCOLEN HP was tested with rats. An LC50 of 5.16 mg/l (4 h) was measured.

Justification for classification or non-classification

The test item needs not to be classified according to regulation (EC) No. 1272/2008 based on the results of tests on acute toxicity.