Magnesium acrylate

Endpoint summary

Description of key information

The data for the toxicity after repeated oral and inhalative administration are taken from a fully reliable studies with administraion of acrylic acid. Acrylic acid is the corresponding organic acid of Magnesium acrylate. The toxic effects of Acrylic acid are mainly caused by its irritating properties. In contrast to the free organic acid Magnesium acrylate has nearly no irritating properties as the studies for irritation and corrosion show.  As the effect levels of acrylic acid are mainly determined by its irritating properties a read across to Magnsium acrylate will overestimate the toxicity. That means the effect levels of Magnesium acrylate should be considerably higher. Therefore the results of the studies with acrylic acid can be taken as a worst case to evaluate the oral and inhalative repeated dose toxicity of Magnesium acrylate.
Acrylic acid:
- NOEL after 90 day oral administration via drinking water to rats: 40 mg/kg bw/d (male rats), 83 mg/kg bw/d (female rats)
- NOAEC for systemic effects after  90 day inhalative exposure to rats:  75 mg/m³
There exist only one study with acute dermal application of Magnesium acrylate. In this study Magnesium acrylate was applied to the skin of rats uniformly over a skin area of 4x4 cm² and the test area was bandaged for an exposure time of 24 hours.  No signs of toxicity whatsoever were seen. On the other hand the dermal application of Acrylic acid caused markable irritation to the skin. 
The European Union Risk Assessment Report Acrylic Acid, Volume 28 ISBN 92-894-1272-0 (EU, 2002) cites a 13 week dermal toxicity study with mice. Mice were treated with 4% , 1% and 0% acrylic acid in acetone on 3 days per week for 13 weeks. While skin irritation became prevalent with 4% acrylic acid, no irritant effect was evident after long-term application of 1% acrylic acid solution. This should be also true for solutions of Magnesium acrylate.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

other: Experimental study with acrylic acid (structural analogue) which is used for read-across (see attached read across justification document in IUCLID section 13)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented, acceptable study report. Justification for read-across: similar chemical structure (see Cemical Safety Report)

Principles of method if other than guideline:

Groups of 15 Fischer 344 rats/sex/dose were administered acrylic acid in the drinking-water at doses of 83, 250, and 750 mg/kg bw/day over a study period of 3 months.

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Microbiological Associates, Inc., Walkersville, MD
- Age at study initiation: 41 days
- Weight at study initiation: males: 105-142 g; females: 81-110 g
- Housing: 3 males or 5 females/cage
- Diet (ad libitum): Zeigler Brothers NIH-07 Rat and Mouse Ration
- Water (ad libitum): tap water originating from the Beaver Run Reservoir, Westmoreland County, PA

Route of administration:

oral: drinking water

Vehicle:

water

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
Fresh test solutions were prepared each week, with the percentage of acrylic acid in the water adjusted to maintain a relatively constant dosage level in g/kg bw.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The stability of aqueous solutions of acrylic acid was determined using a gas chromatographic procedure. Samples were stored for up to 3 weeks at room temperature with aliquots tested for acrylic acid content at frequent intervals. Stability of acrylic acid was determined for solutions stored in standard glass bottles as well as dosing solutions stored in water bottles under actual study conditions. In addition, the concentration of acrylic acid in the dosing preparations was determined monthly during the study.
Aqueous solutions of acrylic acid were found to be stable for at least 3 weeks when stored at room temperature. Solutions stored in animal water bottles were stable for at least 1 week.

Duration of treatment / exposure:

90 days

Frequency of treatment:

continuously

Remarks:

Doses / Concentrations:
83, 250, and 750 mg/kg bw/d
Basis:
nominal in water

No. of animals per sex per dose:

15

Control animals:

yes, concurrent no treatment

Details on study design:

Post-exposure period: none

Positive control:

none

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily


BODY WEIGHT: Yes
- Time schedule for examinations: weekly


FOOD CONSUMPTION:
- Food consumption for cage determined: Yes, weekly



WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: weekly


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: Yes
- Time schedule for collection of blood: approx. 2 weeks before sacrifice
- Anaesthetic used for blood collection: No
- Animals fasted: Yes
- How many animals: 15
- Parameters examined: red and white blood cell counts (RBC and WBC), measurement of hemoglobin, calculation of hematocrit and differential and reticulocyte counts.


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: approx. 2 weeks before sacrifice
- Animals fasted: Yes
- How many animals: 15
- Parameters examined: measurement of serum concentration of total cholesterol (CHOL), serum urea nitrogen, glucose, alkaline phosphatase (ALP), aspaitate transaminase (AST), alanine transaminase (ALT) and creatine phosphokinase (CPR).


URINALYSIS: Yes
- Time schedule for collection of urine: approx. 2 weeks before sacrifice
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No data
- Parameters examined: specific gravity, pH, protein, glucose, ketone, bilirubin, occult blood, nitrite, color and turbidity.


NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
All rats were given a complete gross necropsy examination and organ weights were recorded for the liver, kidneys, heart, spleen, brain and testes.

HISTOPATHOLOGY: Yes
The following tissues were taken and fixed in 10 % neutral buffered formalin:
Pituitary*, Thyroids*, Parathyroids*, Adrenals*, Heart*, Great vessels - Aorta, Thymus*, Spleen*, Cervical lymph node, Uterus, Cervix, Vagina, Vulva, Testes*, Epididymides*, Prostate, Seminal vesicles, Rectum, Kidneys*, Bronchial lymph node, Mesenteric lymph node*, Mediastinal lymph node, Nasal cavity*, Larynx, Trachea*, Lungs*, Ovaries*, Oviduct*, Liver*, Pancreas*, Brain*, Spinal cord, Sciatic nerve, Eyes*, Extraorbital lacrimal gland, Harderian gland, Inner and middle ears, Skin*, Urinary bladder*, Mammary gland*, Tongue*, External ear, Submandibular salivary gland, Adipose tissue, Parotid salivary gland, Sternal bone marrow, Sublingual salivary gland, Gastrocnemius muscle, Esophagus*, Stomach*, Duodenum*, Jejunum, Ileum, Cecum, Colon*, Anterior thigh muscle, Knee joint, Femur, Costochondral junction, Sternum*, Vertebrae, Any lesions*.

The tissues marked with *, as well as any other tissues with gross lesions, were etamined microscopically on all high dose and control animals. Only those tissues with gross lesions were examined microscopically from the intermediate and low level animals.

Statistics:

For every experimental parameter measured, the results of each of the three test levels (high, medium, low) were compared with the control group. To evaluate the statistical significance of possible changes in continuous data, the analysis of variance (ANOVA) validated by Bartlett's test for homogeneity of variance, was used. Individual mean differences were identified by Duncan's multiple range test when indicated by a significant F value for ANOVA. In the case of heterogenous variances, as indicated by Bartlett's test, the Paired group F test, and either the Cochran or the Student t-test were used to identify significant differences. Enumerative data were evaluated statistically by NxR Chi Square test; differences between groups were delineated by Fisher's Exact test. Non-parametric data were compared by a distribution-free multiple comparison method. The fiducial limit of 0.05 was employed as the critical level of difference not attributable to chance.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

effects observed, treatment-related

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
There were no deaths in the three-month study period. No clinical signs were observed in any of the animals.


BODY WEIGHT AND WEIGHT GAIN
Body weight gain was depressed markedly for both sexes at the high dosage level. This effect was statistically highly significant in these groups throughout the study. Further examination shows statistical reduction of body weight gain for the intermediate level males at 4 of the 10 comparison intervals and for the females from 41 through 90 doses.


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Significant reductions in diet consumption were observed for both sexes at the high dosage level.


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
There was a dose-related reduction in water consumption for all male test animals and for females at the high and intermediate levels as well. Water consumption for the low level males, while statistically significant, was numerically close to that of the controls. Furthermore, in a previous study by the same laboratory (Report 42-558), water consumption in male rats receiving as much as 420 mg/kg bw/day of acrylic acid in the drinking water was
numerically and statistically equivalent to the controls. Therefore, the change in water consumption observed for the low level male rats is not considered to be toxicologically important.


HAEMATOLOGY
The only significant finding was an elevation of the red blood cell count for the low level females. This change was not dose-related and is not considered biologically important; it is probably an artifact.


CLINICAL CHEMISTRY
An increase in serum urea nitrogen was noted for the high level male rats. In the females, a decrease of serum cholesterol and increases of serum urea nitrogen, glucose, alkaline phosphatase and aspartate transaminase were observed among the high dosage level animals. In addition, dosage-related increases of serum urea nitrogen and alkaline phosphatase and a decrease in serum cholesterol were observed at the intermediate dosage level for the females.


URINE ANALYSIS
In both sexes at the high and intermediate levels, increases of urine specific gravity and urine protein were observed. A decrease in urine pH was noted for the high level female rats as well. Alterations in fluid balance resulting from decreased fluid intake may underlie the changes in serum urea nitrogen, urine specific gravity and urine protein. An alternate explanation of direct or indirect renal toxicity supported by increased relative kidney weights in both sexes at the high and intermediate levels is possible.


ORGAN WEIGHTS
The effect of acrylic acid on the organ weights of the rats was obvious in the high dosage level in both sexes.

In the male rats this effect included:
(1) Significant reduction in absolute liver, spleen, heart and brain weights.
(2) Significant increase in relative (as % of body weight) liver, kidney, spleen, brain and testes weights.

In the female rats, the effects on the organ weights at the high dose level included:
(1) Significant reduction in absolute liver, spleen and heart weights.
(2) Significant increase in absolute kidney weight and relative kidney and brain weights.

Furthermore, the significant increases in relative kidney and testes weights for the intermediate level males and absolute and relative kidney weights for the intermediate level females are dose-related deleterious effects.


GROSS PATHOLOGY
No significant treatment related gross lesions were noted in any animal on the study.


HISTOPATHOLOGY: NON-NEOPLASTIC
No significant difference in prevalence of microscopic lesions was noted between animals treated with acrylic acid and controls. Malacia within the optic nerves was observed in 2/15 high dose males versus 0/15 control males (P = 0.48) and 1/15 high dose females versus 0/15 control females (P = 1.00). The true prevalence of this lesion in the study could not be determined. However, the unilaterality of this lesion concomitant with absence of lesions within the spinal cord and sciatic nerve indicate that this lesion is not attributable to the treatment with acrylic acid.

Dose descriptor:

NOAEL

Effect level:

83 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: Diet and water consumption, body and organ weight changes and abnormal clinical chemical and urine analysis parameters

Dose descriptor:

LOAEL

Effect level:

250 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: Diet and water consumption, body and organ weight changes and abnormal clinical chemical and urine analysis parameters

Critical effects observed:

not specified

Deleterious effects were observed at the high dosage level (750 mg/kg bw/day) and at the intermediate level (250 mg/kg bw/day) in both sexes. These effects included diet and water consumption, body and organ weight changes and abnormal clinical chemical and urinalysis parameters. At the low dosage level (83 mg/kg bw/day), a significant reduction in water consumption was noted for the male rats. Since this effect is only a moderate reduction of water intake and since the variance is relatively small, the toxicological significance is considered minimal. The slight increase in red blood cells noted for the low dosage level females is considered to be an artifact. Accordingly, the maximum no ill-effect level for three-month ingestion of acrylic acid in the rat is estimated to be at or slightly lower than 83 mg/kg bw/day. Based on this consideration and the findings concerning the effect of acrylic acid at the intermediate and high levels, the minimum effect level is estimated to be 250 mg/kg bw/day.

Summary of results of 90 days of inclusion of Acrylic acid in the drinking water of male rats:

 

Dosage goal [mg/kg bw/d]	750		250		83		control
	Mean	SD	Mean	SD	Mean	SD	Mean	SD
Dosage attained [mg/kg bw/d]	740	50	250	10	84	4	0	0
Diet consumption [g/kg bw/d]	14.0***	0.6	16.2	0.6	16.4	0.9	16.9	0.6
Water consumption [mL/rat/d]	13.0***	0.7	17.5***	0.8	19.4**	1.3	21.4	0.7
Body weight gain [g]	141.5***	21.5	188.2	23.5	196.7	17.3	200.6	20.2
Liver weight [g]	9.33***	1.25	11.30	1.64	11.17	0.85	11.08	0.89
Liver wt as % bw	3.52*	0.15	3.61	0.38	3.50	0.15	3.40	0.14
Kidney weight [g]	2.06	0.22	2.20	0.18	2.14	0.16	2.15	0.13
Kidney wt as % bw	0.78***	0.04	0.71***	0.03	0.67	0.03	0.66	0.02
Spleen weight [g]	0.53**	0.05	0.60	0.08	0.61	0.06	0.60	0.06
Spleen wt as % bw	0.20**	0.02	0.19	0.02	0.19	0.02	0.18	0.01
Heart weight [g]	0.71**	0.09	0.81	0.10	0.83	0.08	0.82	0.10
Heart wt as % bw	0.27	0.02	0.26	0.02	0.26	0.02	0.25	0.03
Brain weight [g]	1.74**	0.08	1.81	0.08	1.81	0.08	1.84	0.06
Brain wt as % bw	0.66***	0.05	0.58	0.04	0.57	0.03	0.57	0.03
Testes weight [g]	2.72	0.17	2.82	0.14	2.73	0.14	2.72	0.32
Testes wt as % bw	1.04***	0.06	0.91*	0.07	0.86	0.07	0.84	0.11

* p< 0.05, ** p< 0.01, *** p< 0.001

Summary of results of 90 days of inclusion of Acrylic acid in the drinking water of female rats:

 

Dosage goal [mg/kg bw/d]	750		250		83		control
	Mean	SD	Mean	SD	Mean	SD	Mean	SD
Dosage attained [mg/kg bw/d]	720	50	250	10	84	3	0	0
Diet consumption [g/kg bw/d]	8.7**	0.3	10.2	0.6	10.6	0.2	10.4	0.4
Water consumption [mL/rat/d]	8.6***	0.5	11.8***	0.7	14.9	0.8	15.0	0.7
Body weight gain [g]	48.0***	8.2	68.4*	9.8	82.1	11.1	78.0	10.8
Liver weight [g]	4.91***	0.50	5.61	0.47	5.84	0.57	5.70	0.45
Liver wt as % bw	3.27	0.22	3.29	0.18	3.16	0.14	3.19	0.13
Kidney weight [g]	1.34**	0.10	1.37***	0.07	1.29	0.08	1.24	0.08
Kidney wt as % bw	0.89***	0.04	0.80***	0.06	0.70	0.04	0.69	0.03
Spleen weight [g]	0.37***	0.04	0.43	0.04	0.46	0.05	0.43	0.05
Spleen wt as % bw	0.24	0.02	0.25	0.02	0.25	0.02	0.24	0.02
Heart weight [g]	0.45***	0.04	0.54	0.05	0.55	0.06	0.54	0.07
Heart wt as % bw	0.30	0.02	0.32	0.02	0.30	0.02	0.30	0.03
Brain weight [g]	1.61	0.12	1.68	0.08	1.66	0.10	1.65	0.14
Brain wt as % bw	1.07***	0.09	0.99	0.08	0.90	0.08	0.93	0.10

* p< 0.05, ** p< 0.01, *** p< 0.001

 

 

Conclusions:

The results of this study with acrylic acid can be extrapolated to magnesium acrylate.
Please refer to the justification for read across in the Chemical Safety Report.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

83 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The data are taken from fully reliable studies with acrylic acid - the corresponding organic acid of Magnesium acrylate. In contrast to the free acid Magnesium acrylate has nearly no irritating properties. As the effect levels of acrylic acid are mainly determined by its irritating properties a read across to Magnsium acrylate will overestimate the toxicity. That means the effect levels of Magnesium acrylate should be considerably higher. Therefore the results of the studies with acrylic acid can be taken as a worst case to evaluate Magnesium acrylate.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

221 mg/m³

Study duration:

subchronic

Species:

mouse

Quality of whole database:

The data are taken from fully reliable studies with acrylic acid - the corresponding organic acid of Magnesium acrylate. In contrast to the free acid Magnesium acrylate has nearly no irritating properties. As the effect levels of acrylic acid are mainly determined by its irritating properties a read across to Magnsium acrylate will overestimate the toxicity. That means the effect levels of Magnesium acrylate should be considerably higher. Therefore the results of the studies with acrylic acid can be taken as a worst case to evaluate Magnesium acrylate.

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

other: Experimental study with acrylic acid (structural analogue) which is used for read-across (see attached read across justification document in IUCLID section 13)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Justification for read-across: similar chemical structure (see Cemical Safety Report)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

Principles of method if other than guideline:

Male and female Fischer 344 rats were exposed to 0, 5 , 25 or 75 ppm acrylic acid vapours (corresponding to 0, 0.015, 0.074, 0.221 mg/L) 6 hours per day, 5 days per week, for 13 weeks.

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, MA
- Age at study initiation: 3 weeks
- Fasting period before study: no
- Housing: 22-3/cage
- Diet (ad libitum): standard laboratory diet (Purina Laboratory Chow, Ralston Purina Co., St. Louis, MO) except during exposure
- Water: ad libitum
- Acclimation period: 16 days

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: inhalation chambers (14500 liters) with stainless steel pyramidal-shaped ceilings and epoxy resin-coated walls and floors dynamic airflow conditions
- Source and rate of air: Exposure levels of acrylic acid were generated by pumping liquid acrylic acid at calculated rates into glass vaporization flasks heated to approximately 130°C. Vapours from the flasks were swept into the chamber air supply duct with compressed air and mixed with incoming air by turbulence.
- Temperature, humidity, pressure in air chamber: 21 °C, 50 %, slight negative pressure
- Air flow rate: 2500 liters per minute
- Air change rate: 10 air changes per hour


TEST ATMOSPHERE
- Brief description of analytical method used: The actual concentration of acrylic acid in each chamber was measured 2-3 times per hour (12-15 times daily) by infrared spectrophotometry using a Miran I Infrared Analyzer at a wavelength of 8.9 µm. Prior to initiating exposures, distribution of acrylic acid vapours within the chambers was determined to be uniform within 10 % of the target concentrations.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Percent dimer in the liquid acrylic acid monomer varied between 0.4% and 3.7% during the exposure interval.
Analytical concentrations (mean ± SD): 5.0 ± 0.3 ppm; 25 ± 1 ppm; 75 ± 1 ppm

Duration of treatment / exposure:

90 days

Frequency of treatment:

6 hours/day; 5 days/week

Remarks:

Doses / Concentrations:
0, 5, 25, or 75 ppm (0, 0.015, 0.074, 0.221 mg/L)
Basis:
analytical conc.

No. of animals per sex per dose:

15

Control animals:

yes, sham-exposed

Details on study design:

Post-exposure period: none

Positive control:

none

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily


BODY WEIGHT: Yes
- Time schedule for examinations: on the 1st day of exposure and weekly thereafter


OPHTHALMOSCOPIC EXAMINATION: YES


HAEMATOLOGY: Yes
- Time schedule for collection of blood: 1 week prior to sacrifice
- Anaesthetic used for blood collection: No
- Animals fasted: Yes / No / No data
- How many animals: 10/sex/dose group
- Parameters examined: Packed Cell Volume (PCV), Hemoglobin (Hgb), Erythrocyte count and morphology, Total and differential leukocyte counts


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the time of sacrifice
- Animals fasted: Yes
- How many animals: 10/sex/dose group
- Parameters examined: Glucose, Blood urea nitrogen (BUN), Alkaline Phosphatase (AP), Glutamic-pyruvic transaminase (SGPT), Total Protein, Albumin, Albumin/Globulin (A/G) Ratio


URINALYSIS: Yes
- Time schedule for collection of urine: 1 week prior to sacrifice
- Metabolism cages used for collection of urine: No
- Animals fasted: No
- Parameters examined: Bilirubin, pH, Glucose, Protein, Ketone, Urobilinogen, Occult Blood, Specific Gravity (refractive ìndex)


NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
Approximately 18 hours after the final exposure, animals were sacrificed and submitted to necropsy. Animals were fasted overnight prior to sacrifice. Each animal was examined externally and internally for gross pathologic alterations. Immediately after decapitation, the eyes of each animal were examined by a glass slide technique with fluorescent illumination. Weights of brain, heart, liver, kidneys and testes were determined and recorded. Lungs and trachea were removed as a unit and the lungs were expanded to approximately their normal inspiratory volume with buffered 10 % formalin.
Animals which died spontaneously or which were sacrificed in a moribund condition during the course of the study were given a complete gross pathological examination. In general, representative portions of the organs and tissues listed below from each animal were preserved in buffered 10 % formalin.


HISTOPATHOLOGY: Yes
Slides (hematoxylin and eosin stained) were prepared and histopathologic examinations performed on tissues listed below for 10 animals of each
sex in the control and 75 ppm exposure groups. Similar histopathologic examinations were conducted on all animals that died spontaneously during the course of the study. Target organs identified in the 75 ppm exposure group were also examined for 10 animals in the 5 ppm and 25 ppm exposure groups.

Organs/Tissues:
adipose tissue, adrenals, aorta, brain, cecum, esophagus, eyes, gonads, gross lesions, heart, small intestine, large intestine, kidneys, lacrimal gland, larynx, liver, lungs, lymph nodes (mesenteric & thoracic), mammary gland, nasal turbinates, pancreas, peripheral nerve, pituitary, prostate, salivary gland, seminal vesicles & coagulating glands, skeletal muscle, skin, spinal cord, spleen, stomach, tongue, trachea, thymus, thyroid/parathyroid, urinary bladder, uterus, vertebrae with bone marrow, zymbal gland

Statistics:

Variances of group body weight changes were analyzed for Bartlett's test for homogeneity of variances (Snedecor and Cochran, 1967). Body weight changes, organ weights, organ-to-body weight ratios, haematology values, clinical chemistry values and urinary specific gravity were evaluated by analysis of variance; differences between control and treatment groups were delineated by Dunnett's test (Steel and Torrie, 1960). The level of significance chosen in all cases was p<0.05.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
Animal observations revealed no discernible effects on appearance or demeanor of rats which were related to exposure. There were no spontaneous deaths of rats during the study.

BODY WEIGHT AND WEIGHT GAIN
Mean body weight gains of male and female rats in the 5, 25 and 75 ppm exposure groups were not different from controls except during the first
two weeks of exposure when the body weight gains of female rats in the 5 and 25 ppm groups were statistically higher than for controls. Thus exposure to 5, 25 or 75 ppm acrylic acid vapors had no adverse effect on growth of male or female rats.


HAEMATOLOGY
There were no statistical differences, in hematologic values of male rats or female rats exposed to acrylic acid vapours which were considered
to be related to exposure. The reduced white cell count for male rats in the 25 ppm group was considered to be a spontaneous statistical difference unrelated to exposure in view of the absence of any effect on white cell count for animals in the higher (75 ppm) exposure group.


CLINICAL CHEMISTRY
Mean alkaline phosphatase values of female rats in the 75 ppm group were significantly higher than for controls; this effect may have been related to exposure but is of uncertain toxicologic significance. All other differences in clinical chemistry parameters of rats (glucose values) were considered to be spontaneous statistical differences unrelated to exposure due to the absence of a dose-response relationship.

URINALYSIS
There were no discernible effects on urinalysis parameters of male or female rats. Statistical analyses of urinary specific gravity values revealed no significant differences between control and exposure groups of rats.


ORGAN WEIGHTS
There were no effects on organ weights or organ-to-body weight ratios of male or female rats which were considered to be related to exposure. All statistical differences in absolute and relative organ weights between control and exposure groups of rats, including absolute and relative liver weights of male rats in the 5 ppm group and relative liver weights of female rats in the 5 ppm group were considered spontaneous in nature and unrelated to exposure to the test material.


GROSS PATHOLOGY
There were no gross pathologic observations which were considered to be related to treatment with the test material. All gross pathologic observations on the male and female rats in this study were considered to be spontaneous in nature and typical of those usually encountered in rats of this strain and age.


HISTOPATHOLOGY: NON-NEOPLASTIC
Histopathologic lesions of the nasal mucosa were observed in 7/10 male and 10/10 female rats in the 75 ppm exposure group but not in rats in the 25 or 5 ppm exposure groups; these were the only lesions considered to be related to treatment. In affected rats in the 75 ppm exposure group, the nasal lesions consisted of slight focal degeneration of the olfactory epithelium on the dorsomedial aspect of the nasal passages. The nasal lesions in most affected rats were detected only in the most rostral of four cross sections obtained through the nasal. However, lesions were observed in the more caudal sections in a few cases. The lesions were characterized principally by disorganization of the normal arrangement of the nuclei of the olfactory epithelium and associated mild degenerative alterations of the epithelial cells in the affected regions. No lesions of the nasal mucosa were observed in 3/10 male rats in the 75 ppm group. Since it was possible that the original sections prepared for these rats were not through the proper portion of the nasal passages, additional sections were prepared. Examination of these additional sections also failed to reveal any discernible lesions. As indicated above, no lesions of the nasal mucosa were observed in either male or female rats in the groups exposed to 25 or 5 ppm acrylic acid. Slight
subacute inflammatory lesions were observed in the nasal mucosa of one female rat in the control group. These lesions were unlike the lesions observed in the rats in the 75 ppm group. All other observations were considered to be spontaneous in nature and unrelated to treatment with the test material.

Dose descriptor:

NOAEC

Effect level:

0.074 mg/L air (analytical)

Sex:

male/female

Basis for effect level:

other: Local effects

Dose descriptor:

LOAEC

Effect level:

0.221 mg/L air (analytical)

Sex:

male/female

Basis for effect level:

other: Local effects: focal degeneration of the olfactory epithelium

Dose descriptor:

NOAEC

Effect level:

0.221 mg/L air (analytical)

Sex:

male/female

Basis for effect level:

other: Systemic toxicity

Critical effects observed:

not specified

Conclusions:

The results of this study with acrylic acid can be extrapolated to magnesium acrylate.
Please refer to the justification for read across in the Chemical Safety Report.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

74 mg/m³

Study duration:

subchronic

Species:

mouse

Quality of whole database:

The data are taken from fully reliable studies with acrylic acid - the corresponding organic acid of Magnesium acrylate. In contrast to the free acid Magnesium acrylate has nearly no irritating properties. As the effect levels of acrylic acid are mainly determined by its irritating properties a read across to Magnsium acrylate will overestimate the toxicity. That means the effect levels of Magnesium acrylate should be considerably higher. Therefore the results of the studies with acrylic acid can be taken as a worst case to evaluate Magnesium acrylate.

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Study duration:

subchronic

Species:

rat

Quality of whole database:

Repeated dose toxicity studies are available for oral and inhalative route of administration with Acrylic acid, the substance used for read across. Even if a dermal exposition to Magnesium acrylate may occur the most suitable way to determine the systemic toxicity of the test substance is normally oral administration. Further it can be concluded from the low acute dermal toxicity of Magnesium acrylate that the dermal resorption of Magnesium acrylate is relatively small. Additionally the metabolism studies show a fast elemination of the acrylic acid from the body. In consequence this will prevent that toxic levels in the body are reached.
However in the European Union Risk Assessment Report Acrylic Acid, Volume 28ISBN 92-894-1272-0 (EU, 2002) a 13 week dermal toxicity study with mice is cited. Mice were treated with 4% , 1% and 0% acrylic acid in acetone on 3 days per week for 13 weeks. While skin irritation became prevalent with 4% acrylic acid, no irritant effect was evident after long-term application of 1% acrylic acid solution.
Effect level:
NOAEL = 1 % acrylic acid solution.

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Study duration:

subchronic

Species:

rat

Quality of whole database:

Repeated dose toxicity studies are available for oral and inhalative route of administration with Acrylic acid, the substance used for read across. Even if a dermal exposition to Magnesium acrylate may occur the most suitable way to determine the systemic toxicity of the test substance is normally oral administration. Further it can be concluded from the low acute dermal toxicity of Magnesium acrylate that the dermal resorption of Magnesium acrylate is relatively small. Additionally the metabolism studies show a fast elemination of the acrylic acid from the body. In consequence this will prevent that toxic levels in the body are reached.
However in the European Union Risk Assessment Report Acrylic Acid, Volume 28ISBN 92-894-1272-0 a 13 week dermal toxicity study with mice is cited. Mice were treated with 4% , 1% and 0% acrylic acid in acetone on 3 days per week for 13 weeks. While skin irritation became prevalent with 4% acrylic acid, no irritant effect was evident after long-term application of 1% acrylic acid solution.

Additional information

There exists no studies with repeated dermal application of Magnesium acrylate. Neverthless the existing data permit an extrapolation on the toxicity of Magnesium acrylate after repeated dermal application: In an acute dermal toxicity study with rats Magnesium acrylate was applied to the skin of rats uniformly over a skin area of 4x4 cm² and the test area was bandaged for an exposure time of 24 hours.  No signs of skin irritation were observed at the site of application. Symptoms of systemic toxicity or unusual findings after application of 2000 mg/kg body weight were not recorded at any time during the study. No death occurred. Body weight development of the animals remained positive 7 days and 14 days post application. The necropsy 14 days after dermal application showed no macroscopic visible substance related pathologic findings. On the other hand the dermal application of Acrylic acid caused markable irritation to the skin. The studies on the metabolism of Acrylic acid revealed, that Acrylic acid is metabolized in the body relatively fast. This should be also true for the Acrylic acid part of Magnesium acrylate.

As studies on irritation/corrosion demonstrated, Magnesium acrylate has only weak irritative effects to the eyes/mucous membranes. So the skin remains intact after a dermal application of Magnesium acrylate. This will result in a limitation of the resorption through the skin. The resorption is further reduced by the higher molecular weight of Magnesium acrylate in comparison to Acrylic acid.

So it is followed that Magnesium acrylate will not reach toxic levels in the body even after repeated dermal application. This assumption is backed by the reults of a repeated dermal toxicity study cited in the European Union Risk Assessment Report Acrylic Acid, Volume 28ISBN 92-894-1272-0 (EU, 2002). Mice were treated with 4% , 1% and 0% acrylic acid in acetone on 3 days per week for 13 weeks. While skin irritation became prevalent with 4% acrylic acid, no irritant effect was evident after long-term application of 1% acrylic acid solution. No sytemic toxicity was found. This should be also true for solutions of Magnesium acrylate.

So it is followed that after repeated dermal application Magnesium acrylate will have no other effects than those seen after single dermal application.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
key study, no systemic effects were observed up to and including the highest dosages.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
key study, no systemic effects were observed up to and including the highest concentration

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
key study

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
Effect level:
NOAEL = 1 % acrylic acid solution.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
Effect level:
NOAEL = 1 % acrylic acid solution.

Justification for classification or non-classification

Studies with a repeated oral or inhalative administration of the corresponding organic acid, acrylic acid, showed only toxic effects caused by the irritating properties of the test substance. No effects were observed in the available repeated dose toxicity studies that fullfil the criteria for classification and labelling according to regulation (EC) 1272/2008, EEC Directives 67/548 and 1999/45

e.g. on specific target organ toxicity.